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mRNA 3′ end processing and more—multiple functions of mammalian cleavage factor I‐68

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Abstract The formation of defined 3′ ends is an important step in the biogenesis of mRNAs. In eukaryotic cells, all mRNA 3′ ends are generated by endonucleolytic cleavage of primary transcripts in reactions that are essentially posttranscriptional. Nevertheless, 3′ end formation is tightly connected to transcription in vivo, and a link with mRNA export to the cytoplasm has been postulated. Here, we briefly review the current knowledge about the two types of mRNA 3′ end processing reactions, cleavage/polyadenylation and histone RNA processing. We then focus on factors shared between these two reactions. In particular, we discuss evidence for new functions of the mammalian cleavage factor I subunit CF Im68 in histone RNA 3′ processing and in the export of mature mRNAs from the nucleus to the cytoplasm. WIREs RNA 2011 2 79–91 DOI: 10.1002/wrna.35 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Processing > 3' End Processing RNA Export and Localization > Nuclear Export/Import

cis‐Acting elements controlling 3 end processing of animal polyadenylated pre‐mRNA (top) and replication‐dependent histone pre‐mRNA (bottom). Sequence elements are designated in black. The main trans‐acting factors recognizing these RNA elements are shown in red. Vertical arrows indicate the processing sites.

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Roles of CF Im68 in cleavage/polyadenylation (left) and histone RNA 3 end processing (right). (a) For polyadenylated transcripts, CF Im plays a co‐transcriptional role. Bound to the transcribing polymerase, it contacts SR proteins and other splicing factors and helps to orchestrate spliceosome assembly. Through its interactions with cleavage and polyadenylation specificity factor (CPSF), it keeps the polymerase‐bound 3 processing factors from binding to and processing wrong sites in the nascent transcript. At this stage, CF Im is presumably un‐ or hypophosphorylated. (b) Upon binding to UGUA sequences in the nascent transcript, CF Im gets phosphorylated (orange P), and assumes a role in 3‐terminal exon definition and poly(A) site selection through its interactions with splicing factors and the CPSF component Fip1. Splicing of the last intron and cleavage/polyadenylation take place. (c) After cleavage/polyadenylation has occurred, CF Im binds to the exon junction complex (EJC) via SR proteins and to NXF and thereby couples 3 end processing to nucleocytoplasmic transport. (d) For replication‐dependent histone mRNAs, a coupling of 3 end processing to transcription via binding of processing factors to the polymerase has not been described. (e) Bound to the U7 snRNP protein Lsm11, CF Im68 mediates the binding of the heat‐labile processing factor through interactions with splicing factors and the U2 snRNP bound to an RNA element in the histone open reading frame and to the CPSF component Fip1, and thereby facilitates histone RNA 3 end processing. (f) A role in histone mRNA export from the nucleus has not been proven, but CF Im68 is associated with some mature mRNA, presumably through SR proteins bound to the internal sequence. See text for details and note that several aspects of this scheme of events remain to be demonstrated.

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Domain organization and interactions of cleavage factor Im subunits CF Im25 (a) and CF Im68 (b).

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Browse by Topic

RNA Export and Localization > Nuclear Export/Import
RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
RNA Processing > 3′ End Processing

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