Evidence that all messenger RNA molecules (except histone messenger RNA) contain poly(A) sequences and that the poly(A) has a nuclear function

Adesnik, Milton; Salditt, M.; Thomas, William; Darnell, James

doi:10.1016/0022-2836(72)90397-x

Cited by 354 publications

(91 citation statements)

References 12 publications

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“…RNase digestion (pancreatic RNase cuts at C and U residues, while T1 RNase cuts at G) of this mRNA preparation revealed a resistant fraction presumed to be poly(A) (Lim and Canellakis 1970;Edmonds et al 1971;Adesnik et al 1972;Mendecki et al 1972;Birnboim et al 1973). Since long poly(A) tracts were not thought to be DNA-templated (Birnboim et al 1973;Jelinek et al 1973), a poly(A) polymerase was sought and found that was subsequently shown to be responsible for poly(A) tail formation on mRNA (Winters and Edmonds 1973a,b).…”

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

confidence: 94%

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

Proudfoot¹

2011

Genes Dev.

519

486

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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.

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

confidence: 94%

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

Proudfoot¹

2011

Genes Dev.

519

486

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“…With only one known exception, all eukaryotic mRNAs are posttranscriptionally modified at their 39 ends by addition of a poly(A) tail (Adesnik et al+, 1972)+ Poly(A) tails are generated in the nucleus in a two-step reaction that involves cleavage of the nascent transcript and subsequent polyadenylation of the upstream RNA fragment (reviewed by Colgan & Manley, 1997;Kühn & Wahle, 1997)+ After transport of mature mRNAs to the cytoplasm, poly(A) tails increase the efficiency of translation initiation and help to stabilize the mRNAs (Beelman & Parker, 1995;Sachs et al+, 1997)+ Presumably after interaction with the translational apparatus, poly(A) tails are shortened by a deadenylation mechanism that triggers the decay of the mRNA (Beelman & Parker, 1995)+ The formation of poly(A) tails in the nucleus involves a number of trans-acting protein factors, namely cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), cleavage factors I m and II m (CF I m and CF II m ), poly(A) polymerase (PAP), and poly(A)-binding protein (PABP)+ Specific RNA-protein contacts and protein-protein interactions cause the assembly of these factors with the RNA substrate, generating a multicomponent 39-end-processing complex (reviewed by Keller, 1995;Manley, 1995;Kühn & Wahle, 1997)+ The precursor RNA (pre-mRNA) is first endonucleolytically cleaved at a particular phosphodiester bond, and the resulting 39-OH group then receives approximately 250 adenylate residues+ The polyadenylation reaction is catalyzed by poly(A) polymerase, but this enzyme by itself has a very low and unspecific affinity for RNA+ In the 39-end-processing complex, poly(A) polymerase must interact with CPSF to be tethered to the primer+ However, poly(A) synthesis in the presence of poly(A) polymerase and CPSF is slow and inefficient+ Processive and efficient polymerization requires an additional factor, the poly(A)-binding protein+…”

Section: Introductionmentioning

confidence: 99%

Deciphering the cellular pathway for transport of poly(A)-binding protein II

Calado

Kutay

Kühn³

et al. 2000

RNA

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Poly(A)-binding protein II (PABP2)is an abundant nuclear protein that binds with high affinity to nascent poly(A) tails, stimulating their extension and controlling their length. In the cytoplasm, a distinct protein (PABP1) binds to poly(A) tails and participates in mRNA translation and stability. How cytoplasmic PABP1 substitutes for nuclear PABP2 is still unknown. Here we report that PABP2 shuttles back and forth between nucleus and cytoplasm by a carrier-mediated mechanism. A potential novel type of nuclear localization signal exists at the C-terminus of the protein, a domain that is highly enriched in methylated arginines. PABP2 binds directly to transportin in a RanGTP-sensitive manner, suggesting an involvement of this transport receptor in mediating import of the protein into the nucleus. Although PABP2 is small enough to diffuse passively through the nuclear pores, protein fusion experiments reveal the existence of a facilitated export pathway. Accordingly, no transport of PABP2 to the cytoplasm occurs at 4 8C. In contrast, export of PABP2 continues in the absence of transcription, indicating that transport to the cytoplasm is independent of mRNA traffic. Thus, rather than leaving the nucleus as a passive passenger of mRNAs, the data suggest that PABP2 interacts with the nuclear export machinery and may therefore contribute to mRNA transport.

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“…The investigation of eukaryotic mRNA has focussed on molecules that possess a 3'-terminal poly(A) seg ment [l-3] since they can be isolated easily by virtue of their high affinity for oligo(dT)-cellulose [4,5], poly(U)-Sepharose [6,7] or Millipore filters [8]. The possible functions of the poly(A) tracts in terms of nuclear and cytoplasmic events have been extensively reviewed [2,3,.…”

Section: Introductionmentioning

confidence: 99%

“…The possible functions of the poly(A) tracts in terms of nuclear and cytoplasmic events have been extensively reviewed [2,3,. Recently, however, a considerable body of evidence has accumulated suggesting the presence of mRNA molecules lacking poly(A) (poly(A)-mRNA) as judged by their failure to bind to Millipore filters [8], oligo(dT)-cellulose [14-161 or poly(U)-Sepharose [6,17]. The purpose of this short review is to assess present knowledge of these poly(A)-mRNAs.…”

Section: Introductionmentioning

confidence: 99%