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Curr Opin Struct Biol. 2019 Sep 6;59:143-150. doi: 10.1016/j.sbi.2019.08.001. [Epub ahead of print]

Mechanistic insights into mRNA 3'-end processing.

Author information

1
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
2
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
3
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom. Electronic address: passmore@mrc-lmb.cam.ac.uk.
4
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: jinek@bioc.uzh.ch.

Abstract

The polyadenosine (poly(A)) tail found on the 3'-end of almost all eukaryotic mRNAs is important for mRNA stability and regulation of translation. mRNA 3'-end processing occurs co-transcriptionally and involves more than 20 proteins to specifically recognize the polyadenylation site, cleave the pre-mRNA, add a poly(A) tail, and trigger transcription termination. The polyadenylation site (PAS) defines the end of the 3'-untranslated region (3'-UTR) and, therefore, selection of the cleavage site is a critical event in regulating gene expression. Integrated structural biology approaches including biochemical reconstitution of multi-subunit complexes, cross-linking mass spectrometry, and structural analyses by X- ray crystallography and single-particle electron cryo-microscopy (cryoEM) have enabled recent progress in understanding the molecular mechanisms of the mRNA 3'-end processing machinery. Here, we describe new molecular insights into pre-mRNA recognition, cleavage and polyadenylation.

PMID:
31499460
DOI:
10.1016/j.sbi.2019.08.001

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