Welcome to Nick Proudfoot’s Group Homepage

We study the molecular process that divides one gene from its adjacent gene partners, in particular the mechanism of transcription termination. Far from simply completing the final step in transcribing a gene, termination is now known to directly influence transcriptional initiation by gene looping from promoter to terminator as well as affecting downstream genes by transcriptional interference or in the case of convergent genes by inducing double strand (ds) RNA mediated heterochromatin formation through RNA interference pathways. This process of gene “punctuation” is illustrated in Figure 1 and emphasises the critical nature of gene arrangement along a eukaryotic chromosome. My lab has made major contributions to this field in the last few years which have further extended our understanding of the influence of transcriptional termination on other connected features of gene expression.

FIGURE 1: Gene punctuation

Pol II termination in mammals
We have employed a simple, experimentally tractable RNA polymerase (Pol) II terminator reporter system to substantially resolve the basic termination mechanism in mammalian cells. This involves transient transfection of HeLa cells with minigene plasmid constructs containing variable promoters reading into the small human b-globin gene (comprising 3 exons and 2 introns) and then variable 3’ end formation signals: polyA signals and downstream pause sites or co-transcriptional cleavage (CoTC) sequences. Combined with the analysis of cis elements required for Pol II termination we have also tested specific trans acting termination factors by their selective knock down using RNAi strategies. These studies have revealed that efficient Pol II termination requires both a polyA signal and either a downstream positioned transcriptional pause site [1] or alternatively CoTC sequences [2, 3]. We have shown that pausing Pol II soon after a functional polyA site allows cleavage of template associated nascent transcript at the polyA site and immediate release of mRNA from the transcription site. 5’-3’ exonuclease (Xrn2 – the so called torpedo) degradation then removes transcripts still attached to downstream elongating Pol II and in so doing provokes Pol II release from the gene’s 3’ end [4]. Alternatively the polymerase reads through a downstream CoTC sequence whereupon the transcript is rapidly cleaved at CoTC transcripts before polyA site cleavage has occurred. The exonuclease torpedo then promotes Pol II release by entry at the CoTC site [5]. In this later case a binary complex of Pol II and associated transcript (still not cleaved at the polyA site) is released from the chromatin template. Subsequent cleavage at the polyA site causes the mRNA to release from Pol II [4]. Interestingly this CoTC mediated mechanism causes an enhancement of gene expression (at the protein level), especially when the polyA site is relatively inefficient. Presumably this is because the uncleaved transcript in the released binary complex escapes template associated exosome activity and so allows less efficiently processed

FIGURE 2: CoTC mediated Pol II termination

transcripts (ie with weak polyA or splice sites) more time to mature before exosome degradation occurs [6]. The mechanism of CoTC mediated transcription termination is outlined in Figure 2. This observed CoTC dependent enhancement of gene expression has been patented by our lab through ISIS, the Oxford University IP company. While we have made clear progress in unravelling the mammalian Pol II termination mechanism, many questions about CoTC generality and mechanistic detail of mammalian Pol II termination remain and will be further investigated in our new research programme.

Pol II and Pol I termination in S. cerevisiae
Our recent studies on yeast (S. cerevisiae) Pol II and Pol I termination mechanisms have also significantly advanced understanding of these two processes. As in mammals, Pol II termination relies on a torpedo mechanism to promote polymerase release [7]. However probably due to the close spacing of yeast genes along chromosomes, the only cis termination signals identified for mRNA encoding genes are also polyA signals. The Rat1 (Xrn2 homologue) torpedo appears to only partially promote Pol II termination and requires help from a helicase activity called Sen1 for more efficient termination [8]. These observations lead to the alternative Pol II termination mechanism in yeast mediated by the NRD complex [9, 10]. NRD comprising Nrd1, Nab3 and Sen1 is mainly employed to terminate small Pol II transcribed genes (snoRNA and snRNAs). However its importance has been greatly extended by the discovery of numerous unstable transcripts throughout the yeast genome both between annotated genes as well as within and antisense to annotated genes, all of which employ NRD mediated termination mechanisms [11-13]. We have now established that NRD termination further acts as a failsafe termination mechanism for mRNA encoding genes, especially if the normal torpedo mechanism is impaired (for example by Rat1 inactivation; [14]). Interestingly a third Pol II termination mechanism also operates for mRNA encoding genes which is mediated by the sole RNase III endonuclease of S. cerevisiae, Rnt1. RNA hairpins with a specific tetraloop sequence are cleaved by Rnt1 co-transcriptionally and so promote Pol II termination again by a torpedo mechanism [14, 15]. A clear example of this process is for rDNA genes transcribed by Pol I. Here too an Rnt1 cleavage hairpin sequence at the end of the each rDNA transcription unit is required for Pol I termination, again by a Rat1 mediated torpedo termination mechanism [8, 16].

FIGURE 3: Three ways to terminate nascent Poll II transcripts

The three alternate Pol II termination mechanisms that operate on protein coding genes in S. cerevisiae are summarised in Figure 3. A major question for our future research programme is to determine how one of these three mechanisms is selected for a particular Pol II transcribed gene. It is apparent that the mechanisms of termination employed by Pol I and Pol II are strikingly similar suggesting their high evolutionary conservation. We will further extend our analysis of the Pol I termination mechanism. Furthermore we plan to investigate the basic mechanism of transcription termination in archaeal genes to assess the generality in evolutionary terms of the transcriptional termination mechanism.

Gene looping: generality and mechanistic insight
Following on from our original discovery that at least some genes in S. cerevisiae form transcription dependent gene loops, we have now extended these observations to include numerous further examples of gene loops in a range of eukaryotes. In S. cerevisiae all mRNA encoding genes tested, irrespective of their size (>20 from NJP and M. Hampsey labs) form transcription dependant gene loops [17-19]. Similarly gene looping appears a general characteristic of S. pombe genes (M. Gullerova and N.J. Proudfoot unpublished) as well as in much larger mammalian genes. Thus we have extensively characterised the presence and cis sequence element requirements of HIV-1 provirus [20], BRCA1 [21] and b-globin (H Wijayatilake and N.J.Proudfoot unpublished) gene looping. We predict that all protein encoding Pol II transcribed genes form transcription dependent looped structures. Indeed other gene classes transcribed by different RNA polymerases (yeast Pol I and human mitochondrial polymerases) also form looped structures following activation [22, 23]. Key issues to be resolved about gene looping are firstly what is the function these dynamic structures? Also what are the molecular players that control gene loop formation? Both these questions will be investigated in our new research programme. One recently established function for gene loops comes from our findings on inducible genes in S. cerevisiae [24, 25]. We show that gene loops are connected with the maintenance of transcriptional memory, a process whereby inducible genes, if repressed for only a short period are more rapidly induced when reactivated. Gene loops act to cement inducible genes to the nuclear pore complex (NPC) in such a way that they remain attached for short repression periods allowing more rapid gene expression when re-induced (Figure 4). We will further investigate this NPC association process as well as looking at other ways that gene looping may enhance or regulate gene expression.

FIGURE 4: Gene loops associate with the nuclear pore complex to provide transcriptional memory

Intronic CoTC and microRNA maturation
An interesting aspect of CoTC is the possibility that it operates at other gene locations than in terminator regions. In particular we have considered the possibility that CoTC might operate within the large introns of higher eukaryotes. Here it could enhance splicing by promoting the rapid removal of intronic transcripts that otherwise compete with regular splicing signals and so perturb the normal splicing process. Furthermore intronic transcripts, if not rapidly removed, have the capacity to invade the DNA duplex behind elongating Pol II and so induce R-loop formation. These structures expose the untranscribed DNA as a single strand which leads to DNA damage [26, 27]. We have directly tested the effect of intronic co-transcriptional cleavage by insertion of either a CoTC or ribozyme element. Neither cleavage events affected splicing arguing for an exon tethering mechanism as shown in Figure 5 [28]. Interestingly natural cases of intronic CoTC widely occur as in the case of pri-microRNA maturation. Thus many microRNAs are intron encoded and their excision from the Pol II transcript occurs co-transcriptionally [29].

FIGURE 5: Co-transcriptional cleavage of introns and exon tethering

Convergent gene termination and transient heterochromatin in S. pombe
A major development from our recent research into Pol II termination came from the analysis of convergent genes in S. pombe. Earlier work from our lab had established that the two inducible, highly expressed genes nmt1 and nmt2 unexpectedly generate extended primary transcripts, where Pol II termination occurs several kb past their normal polyA sites [30]. Furthermore these transcripts overlap with convergent genes reading towards nmt1 and nmt2. We have now substantially extended our understanding of these original findings by showing that convergent genes in S. pombe generally produce overlapping transcripts, but that this transcription profile is specific to the G1 cell cycle phase (see Figure 6). dsRNA so produced induces the RNAi gene silencing pathway [31] resulting in transient heterochromatin formation across convergent gene loci in late G1-S phase. This in turn recruits the ring structured cohesin protein to these gene loci which is moved by ongoing transcription into the central intergenic region of convergent gene pairs. This cohesin concentration in effect acts as a road block to further read through transcription. During the rest of the G2 cell cycle phase, convergent genes terminate close to their proximal polyA signals and consequently do not generate dsRNA [32]. These unexpected results open up a new research direction into the use of regulated Pol II termination to control gene expression by transcription induced heterochromatin formation.

FIGURE 6: Cell cycle regulation of convergent gene transcription in S. pombe

References

Gromak, N., S. West, and N.J. Proudfoot, Pause sites promote transcriptional termination of mammalian RNA polymerase II. Mol Cell Biol, 2006. 26(10): p. 3986-96.
Dye, M.J. and N.J. Proudfoot, Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II. Cell, 2001. 105(5): p. 669-81.
West, S., K. Zaret, and N.J. Proudfoot, Transcriptional termination sequences in the mouse serum albumin gene. RNA, 2006. 12(4): p. 655-65.
West, S., N.J. Proudfoot, and M.J. Dye, Molecular dissection of mammalian RNA polymerase II transcriptional termination. Mol Cell, 2008. 29(5): p. 600-10.
West, S., N. Gromak, and N.J. Proudfoot, Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature, 2004. 432(7016): p. 522-5.
West, S. and N.J. Proudfoot, Transcriptional termination enhances protein expression in human cells. Mol Cell, 2009. 33(3): p. 354-64.
Kim, M., N.J. Krogan, L. Vasiljeva, O.J. Rando, E. Nedea, J.F. Greenblatt, and S. Buratowski, The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature, 2004. 432(7016): p. 517-22.
Kawauchi, J., H. Mischo, P. Braglia, A. Rondon, and N.J. Proudfoot, Budding yeast RNA polymerases I and II employ parallel mechanisms of transcriptional termination. Genes Dev, 2008. 22(8): p. 1082-92.
Steinmetz, E.J., N.K. Conrad, D.A. Brow, and J.L. Corden, RNA-binding protein Nrd1 directs poly(A)-independent 3'-end formation of RNA polymerase II transcripts. Nature, 2001. 413(6853): p. 327-31.
Rondon, A.G., H.E. Mischo, and N.J. Proudfoot, Terminating transcription in yeast: whether to be a 'nerd' or a 'rat'. Nat Struct Mol Biol, 2008. 15(8): p. 775-6.
Jacquier, A., The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet, 2009. 10(12): p. 833-844.
Arigo, J.T., D.E. Eyler, K.L. Carroll, and J.L. Corden, Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Mol Cell, 2006. 23(6): p. 841-51.
Vasiljeva, L. and S. Buratowski, Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II transcripts. Mol Cell, 2006. 21(2): p. 239-48.
Rondon, A.G., H.E. Mischo, J. Kawauchi, and N.J. Proudfoot, Fail-safe transcriptional termination for protein-coding genes in S. cerevisiae. Mol Cell, 2009. 36(1): p. 88-98.
Ghazal, G., J. Gagnon, P.E. Jacques, J.R. Landry, F. Robert, and S.A. Elela, Yeast RNase III triggers polyadenylation-independent transcription termination. Mol Cell, 2009. 36(1): p. 99-109.
El Hage, A., M. Koper, J. Kufel, and D. Tollervey, Efficient termination of transcription by RNA polymerase I requires the 5' exonuclease Rat1 in yeast. Genes Dev, 2008. 22(8): p. 1069-81.
O'Sullivan, J.M., S.M. Tan-Wong, A. Morillon, B. Lee, J. Coles, J. Mellor, and N.J. Proudfoot, Gene loops juxtapose promoters and terminators in yeast. Nat Genet, 2004. 36(9): p. 1014-8.
Ansari, A. and M. Hampsey, A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping. Genes Dev, 2005. 19(24): p. 2969-78.
Singh, B.N. and M. Hampsey, A transcription-independent role for TFIIB in gene looping. Mol Cell, 2007. 27(5): p. 806-16.
Perkins, K.J., M. Lusic, I. Mitar, M. Giacca, and N.J. Proudfoot, Transcription-dependent gene looping of the HIV-1 provirus is dictated by recognition of pre-mRNA processing signals. Mol Cell, 2008. 29(1): p. 56-68.
Tan-Wong, S.M., J.D. French, N.J. Proudfoot, and M.A. Brown, Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene. Proc Natl Acad Sci U S A, 2008. 105(13): p. 5160-5.
Martin, M., J. Cho, A.J. Cesare, J.D. Griffith, and G. Attardi, Termination factor-mediated DNA loop between termination and initiation sites drives mitochondrial rRNA synthesis. Cell, 2005. 123(7): p. 1227-40.
Nemeth, A., S. Guibert, V.K. Tiwari, R. Ohlsson, and G. Langst, Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes. Embo J, 2008. 27(8): p. 1255-65.
Laine, J.-P., Singh, B.N., Krishnamurthy, S. and M. Hampsy, A physiological role for gene loops in yeast. Genes Dev., 2009. 23: p. 2604-2609.
Tan-Wong, S.M., Wijayatilake, H. and N.J. Proudfoot, Gene loops function to maintain transcriptional memory through interaction with the nuclear pore complex Genes Dev., 2009. 23: p. 2610-2624.
Li, X. and J.L. Manley, Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell, 2005. 122(3): p. 365-78.
Huertas, P. and A. Aguilera, Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell, 2003. 12(3): p. 711-21.
Dye, M.J., N. Gromak, and N.J. Proudfoot, Exon tethering in transcription by RNA polymerase II. Mol Cell, 2006. 21(6): p. 849-59.
Morlando, M., M. Ballarino, N. Gromak, F. Pagano, I. Bozzoni, and N.J. Proudfoot, Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol, 2008.
Hansen, K., C.E. Birse, and N.J. Proudfoot, Nascent transcription from the nmt1 and nmt2 genes of Schizosaccharomyces pombe overlaps neighbouring genes. EMBO J, 1998. 17(11): p. 3066-77.
Zofall, M. and S.I. Grewal, RNAi-mediated heterochromatin assembly in fission yeast. Cold Spring Harb Symp Quant Biol, 2006. 71: p. 487-96.
Gullerova, M. and N.J. Proudfoot, Cohesin complex promotes transcriptional termination between convergent genes in S. pombe. Cell, 2008. 132(6): p. 983-95.

Research Funding

The lab is supported by a Programme Grant from the Wellcome Trust.

Publications

2012 - Present

E White, K Kamieniarz-Gdula, MJ Dye, NJ Proudfoot AT-rich sequence elements promote nascent transcript cleavage leading to RNA polymerase II termination. Nucleic Acids Res. 41 1797-1806 (2013)

HE Mischo, NJ Proudfoot Disengaging polymerase: Terminating RNA polymerase II transcription in budding yeast Biochim Biophys Acta 1829, 174-185 (2013)

M Gullerova, NJ Proudfoot Convergent transcription induces transcriptional gene silencing in fission yeast and mammalian cells. Nat Struct Mol Biol. 19, 1193-1201 (2012)

SM Tan-Wong, JB Zaugg, J Camblong, Z Xu, DW Zhang, HE Mischo, AZ Ansari, NM Luscombe, LM Steinmetz, NJ Proudfoot Gene loops enhance transcriptional directionality. Science. 38, 671-675 (2012)

T Henriques, Z Ji,SM Tan-Wong, AM Carmo, B Tian, NJ Proudfoot,A Moreira Transcription termination between polo and snap, two closely spaced tandem genes of D. melongaster Transcription. 3, 198-212 (2012)

SE Avendano-Vazquez, A Dhir, S Bembich, E Buratti, N Proudfoot, FE Baralle Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing and alternative polyA site selection Genes Dev. 26, 1679-1684 (2012)

2011

H.E. Mischo, B. Gómez-González, P. Grzechnik, A.G. Rondón, W. Wei, L. Steinmetz, A. Aguilera and N.J. Proudfoot. Yeast Sen1 helicase protects the genome from transcription-associated instability. Mol. Cell 41, 21-32 (2011)

M. Gullerova, D. Moazed and N.J. Proudfoot. Autoregulation of convergent RNAi genes in fission yeast. Genes and Dev. 25, 556-568 (2011)

P.A. Pinto, T. Henriques, M.O. Freitas, T. Martins, R.G. Dominigues, P.S. Wyrzykowska, P.A. Coelho, A.M. Carmo, C.E. Sunkel, N.J. Proudfoot and A. Moreira. RNA polymerase II kinetics and polo polyadenylation signal selection. EMBO J. 12, 2431-2444 (2011)

K. Skourti-Stathaki, N.J. Proudfoot and N. Gromak. Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2 dependent termination. Mol. Cell 42, 794-805 (2011)

N.J. Proudfoot. Ending the message: poly(A) signals then and now. Genes and Dev. 25, 1770-1782 (2011)

2010

I. Kaufmann, E. White, A. Azad, S. Marguarat, J. Bahler and N.J. Proudfoot. Transcription activation of the general amino acid permease gene per1 by the histone deacetylase Clr6 is regulated by Oca2 kinase. Mol. Cell. Biol. 30, 3396-3410 (2010)

P. Braglia, K. Heindl, A. Schleiffer, J. Martinez and N.J. Proudfoot. Role of the RNA/DNA kinase Grc3 in transcription termination by RNA polymerase I. EMBO Reports 11, 758-764 (2010)

P. Braglia, J. Kawauchi and N.J. Proudfoot. Co-transcriptional RNA cleavage provides a failsafe termination mechanism for yeast RNA polymerase I. Nucl. Acids Res. Epub Oct 23^rd (2010)

M. Gullerova and N.J. Proudfoot. Transcriptional interference and gene orientation in yeast: Noncoding RNA connections. CSH Symposium on Quantitatives Biology LXXV (2010)

2009

S.-M.Tan Wong, H.Wijayatilake and N.J.Proudfoot. Gene loops function to maintain transcriptional memory through interaction with the nuclear pore complex. Genes and Dev. 23, 2610-2624 (2009)

M. Ballarino, F. Pagano, G. Erika, M. Morlando, D. Cacchiarelli. M.Marchioni. N.J.Proudfoot and I.Bozzoni.Coupled RNA processing and transcription of intergenic primary miRNAs Mol. Cell. Biol. 36, 88-98 (2009)

A.Rondon, H.E.Mischo, J.Kawauchi and N.J.Proudfoot. Failsafe transcription termination for protein coding genes in S.cerevisiae Molecular Cell 29, 5632-5638 (2009)

C.J.Webby*, A. Wolf*, N.Gromak*, et al., N.J.Proudfoot, C.J.Schofield and A. Bottgar. Jmjd6 catalyses lysyl-hydroxylation of U2AF, a protein associated with RNA splicing. Science 325, 90-93 (2009)

M.Moore and N.J.Proudfoot.Pre-mRNA processing reaches back to transcription and ahead to translation.Cell 136, 688-700 (2009) Review

S.West and N.J.Proudfoot. Transcriptional termination enhances protein expression in human cells. Molecular Cell 33, 354-364 (2009).

2008

K.J.Perkins and N.J.Proudfoot. An ungracious host for an unwelcome guest Cell Host Microbe. Cell Host microbe, 4, 89-91 (2008) Preview

A.G.Rondon and N.J.Proudfoot. Nuclear roadblocks for mRNA export. Cell 135, 207-208 (2008) Preview

A.G.Rondon, H.E.Mischo and N.J.Proudfoot. Terminating transcription in yeast: whether to be a 'nerd' or a 'rat'. Nature Structural Molecular Biology 15, 775-776 (2008). News and Views

M.Morlando, M.Ballarino, N.Gromak, F.Pagano. I.Bozzoni and N.J.Proudfoot. Primary microRNA transcripts are processed co-transcriptionally. Nature Structural and Molecular Biology 15, 902-909 (2008)

J.Kawauchi, H.Mischo, P. Braglia, A.Rondon and N.J.Proudfoot. Budding yeast RNA polymerases I and II employ parallel mechanisms of transcriptional termination. Genes and Dev. 22, 1082-1092 (2008)

S.-M. Tan Wong, J.D. French, N.J. Proudfoot and M.A.Brown. Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene. Proc. Nat. Acad. Sci. 105, 5160-5165 (2008)

M. Gullerova and N.J.Proudfoot. Cohesin complex promotes transcriptional termination between convergent genes in S.pombe. Cell 132, 983-995 (2008)

S.West, N.J.Proudfoot and M.J.Dye. Molecular Dissection of Mammalian RNA Polymerase II Transcriptional Termination. Molecular Cell 29, 600-610 (2008)

K.J.Perkins, M.Lusic, I.Miar, M.Giacca and N.J.Proudfoot. Transcription dependent gene looping of the HIV-1 provirus is dictated by recognition of pre-mRNA processing signals. Molecular Cell 29, 56-68 (2008)

N.Gromak, G.Talotti, N.J.Proudfoot and F.Pagani. Modulating alternative splicing by cotranscriptional cleavage of nascent intronic RNA. RNA 14, 1-8 (2008)

S.West and N.J.Proudfoot. Human Pcf11 enhances degradation of RNA polymerase II-associated nascent RNA and transcriptional termination. Nucl. Acids Res. 36, 905-914 (2008)

2007

M.Gullerova and N.J.Proudfoot. Gene silencing cuts both ways. Cell. 131, 649-651 (2007) Preview

H.S.Jones, J.Kawauchi, P.Braglia, C.M.Alen, N.A.Kent and N.J.Proudfoot. RNA polymerase I in yeast transcribes dynamic nucleosomal rDNA. Nature Structural and Molecular Biology 14, 123-130 (2007)

2006

M.J.Dye, N.Gromak, D.Haussecker, S.West, and N.J.Proudfoot. Turnover and function of noncoding RNA Polymerase II transcripts. CSH Symposium on Quantitative Biology LXXI, 275-284 (2006) Review

A.Binnie, P.Castelo-Branco, J.Monks and N.J.Proudfoot. Transcript-mediated gene pairing in the mammalian nucleus. J. Cell Sci. 119, 3876-3887 (2006)

N.Gromak, S.West and N.J.Proudfoot. Pause sites promote transcriptional termination of mammalian RNA polymerase II. Mol. Cell. Biol. 26, 3986-3996 (2006)

M.J.Dye, N.Gromak and N.J.Proudfoot. Exonic tethering of RNA polymerase II transcripts. Molecular Cell, 21, 849-859 (2006)

S.West, K.Zaret and N.J.Proudfoot. Transcriptional termination sequences in the mouse serum albumin gene. RNA, 12, 655-665 (2006)

S.West, N.Gromak, C.J.Norbury and N.J.Proudfoot. Adenylation and exosome-mediated degradation of co-transcriptionally cleaved pre-mRNA in human cells. Molecular Cell, 21, 437-443 (2006)

2005

D.Haussecker and N.J.Proudfoot. Dicer-dependent nuclear turnover of intergenic transcripts from the b-globin gene cluster. Mol. Cell. Biol. 25, 9724-9733 (2005)

K.E.Plant, M.J.Dye and N.J.Proudfoot. Strong polyadenylation and weak pausing combines to cause efficient termination of transcription in the human Gg-globin gene. Mol. Cell. Biol. 25, 3276-3285 (2005)

M.Ares and N.J.Proudfoot. The Spanish connection: Transcription and mRNA processing get even closer. Cell, 120, 163-166 (2005) Meeting review

2004

A.Teixeira, A.Tahiri-Alaoui, S.West, B.Thomas, A.Ramadass, M.Dye, W.James, N.J.Proudfoot and A.Akoulitchev. Auto-catalytic RNA cleavage in the human b-globin gene transcript promotes transcriptional termination. Nature, 432, 525-529 (2004)

S.West, N.Gromak and N.J.Proudfoot. Human 5’->3’ exonuclease XRN2 promotes transcriptional termination from sites of co-transcriptional cleavage. Nature, 432, 522-525 (2004).

J.M.O’Sullivan, S.-M.Tan-Wong, A.Morillon, B.Lee, J.Coles, J.Mellor and N.J.Proudfoot. Gene loops juxtapose promoters and terminators in yeast. Nature Genetics, 35, 1014-1018 (2004)

N.J.Proudfoot. New perspectives on connecting messenger RNA 3’ end formation to transcription. Curr. Op. in Cell Biol. 16, 272-278 (2004) Review

E.M.Prescott, Y.N.Osheim, H.S.Jones, C.M.Alen, J.G.Roan, R.H.Reeder, A.L.Beyer and N.J.Proudfoot. Functional homology in transcriptional termination by RNA polymerases I and II. Proc. Natl. Acad. USA, 101, 6068-6073 (2004)

P.Castelo Branco, A.Furger, M.Wollerton, C.Smith, A.Moreira and N.J.Proudfoot. Polypyrimidine tract binding protein modulates efficiency of polyadenylation. Mol. Cell. Biol. 24, 4174-4183 (2004)

2003

N.J.Proudfoot. Dawdling polymerases allow introns time to splice. Nature Structural Biology 11, 876-878 (2003)

A.Morillon, N.Karabetsou, J.O’Sullivan, N.Kent, N.J.Proudfoot and J.Mellor. Isw1 chromatin remodeling ATPases coordinate transcription, elongation and termination by RNA polymerase II. Cell, 115 425-435 (2003)

A.Morillon, J.O’Sullivan, A.Azad, N.J.Proudfoot and J.Mellor. Regulation of elongating RNA polymerase II by Forkhead transcription factors. Science, 300, 492-495 (2003)

2002

N.J.Proudfoot and J.O’Sullivan. Polyadenylation: A tail of two complexes. Current Biol.12, R855-R857 (2002) Dispatch

S.J.E.Routledge and N.J.Proudfoot. Definition of transcriptional promoters in the human b-globin locus control region. J. Mol. Biol. 323, 601-611 (2002)

C.Alen, N.A.Kent, H.S.Jones, J.O’Sullivan, A.Aranda and N.J.Proudfoot. A role for chromatin remodeling in transcriptional termination by RNA polymerase II. Molecular Cell, 10, 1441-1452 (2002)

K.Y.Kwek, S.Murphy, A.Furger, B.Thomas, W.O’ Gorman, H.Kimura, N.J.Proudfoot and A.Akoulitchev. U1snRNA associates with the general transcription factor IIH and regulates transcription initiation. Nature Structural Biol. 9, 800-805 (2002).

A.Furger, J.O’Sullivan, A.Binnie, B.Lee and N.J.Proudfoot. Promoter proximal splice sites enhance transcription. Genes and Development, 16, 2792-2799 (2002).

E.M.Prescott and N.J.Proudfoot. Transcriptional collision between convergent genes in budding yeast. Proc. Natl. Acad. USA, 99, 8796-8801 (2002)

N.J.Proudfoot. A.Furger and M.J.Dye. Integrating messenger RNA processing and transcription. Cell, 108, 501-512 (2002) Review

2001

N.J.Proudfoot. Genetic dangers in poly(A) signals. EMBO Rep. 2, 891-892 (2001) Minireview

A.Furger, J.Monks and N.J.Proudfoot. HIV-1 and MoMLV retroviruses adopt radically different strategies to regulate promoter proximal polyadenylation. J. Virol. 75, 11735-11746 (2001)

K.E.Plant, S.J.E.Routledge and N.J.Proudfoot. Intergenic transcription in the human b-globin gene cluster. Mol. Cell. Biol. 21, 6507-6514 (2001)

M. Dye and N.J. Proudfoot. Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II. Cell 105: 669-681 (2001)

A.Aranda, and N.J.Proudfoot. Transcriptional termination factors for RNA polymerase II in yeast. Molecular Cell, 7, 1003-1011 (2001)

D.Barilla, B.L.Lee and N.J.Proudfoot. Cleavage/polyadenylation factor 1A associates with the carboxyl-terminal domain of RNA polymerase II in Saccharomyces cerevisiae. Proc. Natl. Acad. USA, 98, 445-450 (2001)

2000

M.Yonaha and N.J.Proudfoot. Transcriptional termination and coupled polyadenylation in vitro. EMBO J. 19, 3770-3777 (2000)

I.H.Greger, A.Aranda and N.J.Proudfoot. Balancing transcriptional interference and initiation on the Gal7 promoter of S. cerevisiae. Proc. Natl. Acad. USA, 97, 8415-8420 (2000)

N.J.Proudfoot. Connecting transcription to messenger RNA processing. Trends in Biochem. Sci. 294, 290-293 (2000) Review

S.Brackenridge and N.J.Proudfoot. Recruitment of a basal polyadenylation factor by the upstream sequence element of the human Lamin B2 polyadenylation signal.
Mol. Cell. Biol. 20, 2660-2669 (2000)

M.P.Ashe, A.Furger and N.J.Proudfoot. Poly(A) site occlusion in the 5’LTR of the HIV-1 provirus principally depends on the close proximity of U1 snRNP, stem loop 1. RNA, 6, 170-177 (2000)