Coupling Termination of Transcription to Messenger RNA Maturation in Yeast

Self Cite

520

486

Polyadenylation [poly(A)] signals (PAS) are a defining feature of eukaryotic protein-coding genes. The central sequence motif AAUAAA was identified in the mid1970s and subsequently shown to require flanking, auxiliary elements for both 39-end cleavage and polyadenylation of premessenger RNA (pre-mRNA) as well as to promote downstream transcriptional termination. More recent genomic analysis has established the generality of the PAS for eukaryotic mRNA. Evidence for the mechanism of mRNA 39-end formation is outlined, as is the way this RNA processing reaction communicates with RNA polymerase II to terminate transcription. The widespread phenomenon of alternative poly(A) site usage and how this interrelates with pre-mRNA splicing is then reviewed. This shows that gene expression can be drastically affected by how the message is ended. A central theme of this review is that while genomic analysis provides generality for the importance of PAS selection, detailed mechanistic understanding still requires the direct analysis of specific genes by genetic and biochemical approaches.

Section: Polyadenylation Signals and 39 Noncoding Rna (Ncrna) Sequencesmentioning

confidence: 99%

Ending the message: poly(A) signals then and now

Proudfoot¹

2011

Self Cite

520

486

“…This provides a signal for binding many factors involved in 39-end formation, which in turn renders RNAPII competent for termination (Whitelaw and Proudfoot 1986;Logan et al 1987;Connelly and Manley 1988;Birse et al 1997;. In yeast, mutations and conditional depletion of factors involved in pre-mRNA cleavage and polyadenylation, including homologs of CstF-64 (Rna15), CstF-77 (Rna14), Pcf11, CPSF160 (Yhh1), CPSF-73 (Ysh1), and Ssu72, result in read-through at the 39-end of protein-coding genes (Birse et al 1998;Dichtl et al 2002;Steinmetz and Brow 2003;Garas et al 2008). Accordingly, ChIP assays suggest that 39-end processing factors, including Pcf11, Rna14, and Rna15, become associated with the RNAPII EC at the poly(A) site, in a Ser2 phosphorylated CTD-dependant manner (Ahn et al 2004;Kim et al 2004a;Luo et al 2006).…”

Section: Trans-acting Factor Dynamics At the Poly(a) Site Affect Tranmentioning

confidence: 99%

“…In mammals, termination can occur anywhere from a few base pairs to several kilobases downstream from the 39-end of the mature RNA (Proudfoot 1989). RNAPII transcription termination is coupled to 39-end processing of the pre-mRNA (Birse et al 1998;Hirose and Manley 2000;Yonaha and Proudfoot 2000;Proudfoot 2004;Buratowski 2005), and an intact polyadenylation signal has long been known to be necessary for transcription termination of protein-coding genes in human and yeast cells (Whitelaw and Proudfoot 1986;Logan et al 1987;Connelly and Manley 1988).…”

mentioning

confidence: 99%

Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

289

326

Gene transcription in the cell nucleus is a complex and highly regulated process. Transcription in eukaryotes requires three distinct RNA polymerases, each of which employs its own mechanisms for initiation, elongation, and termination. Termination mechanisms vary considerably, ranging from relatively simple to exceptionally complex. In this review, we describe the present state of knowledge on how each of the three RNA polymerases terminates and how mechanisms are conserved, or vary, from yeast to human.

“…Mammalian CPSF (Dantonel et al 1997;McCracken et al 1997b) and CstF (cleavage stimulation factor; McCracken et al 1997b) associate with the CTD of RNA polymerase II and mutations in the CTD that prevent this association lead to disturbed transcription termination (McCracken et al 1997b). In addition, recent mutational studies in yeast have demonstrated that factors involved in pre-mRNA 3Ј-end cleavage are active in directing termination of transcription (Birse et al 1998).…”

mentioning

confidence: 99%

Transcriptional termination in the Balbiani ring 1 gene is closely coupled to 3′-end formation and excision of the 3′-terminal intron

Baurén

Беликов²,

Wieslander³

1998

We have analyzed transcription termination, 3 -end formation, and excision of the 3 -terminal intron in vivo in the Balbiani ring 1 (BR1) gene and its pre-mRNA. We show that full-length RNA transcripts are evenly spaced on the gene from a position 300 bp upstream to a region 500-700 bp downstream of the polyadenylation sequence. Very few full-length transcripts and no short, cleaved, nascent transcripts could be observed downstream of this region. Pre-mRNA with 10-20 adenylate residues accumulates at the active gene and then rapidly leaves from the gene locus. Only polyadenylated pre-mRNAs could be detected in the nucleoplasm. Our results are consistent with the hypothesis that transcription termination occurs in a narrow region for the majority of transcripts, simultaneous with 3 -end formation. Excision of the 3 -terminal intron occurs before 3 -end formation in about 5% of the nascent transcripts. When transcription terminates, 3 cleavage takes place and 10-20 adenylate residues are added, the 3 -terminal intron is excised from additionally about 75% of the pre-mRNA at the gene locus. Our data support a close temporal and spatial coupling of transcription termination and the cleavage and initial polyadenylation of 3 -end formation. Excision of the 3 -terminal intron is highly stimulated as the cleavage/polyadenylation complex assembles and 3 -end formation is initiated.