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Rules that govern UPF1 binding to mRNA 3' UTRs.

Abstract：

:Nonsense-mediated mRNA decay (NMD), which degrades transcripts harboring a premature termination codon (PTC), depends on the helicase up-frameshift 1 (UPF1). However, mRNAs that are not NMD targets also bind UPF1. What governs the timing, position, and function of UPF1 binding to mRNAs remains unclear. We provide evidence that (i) multiple UPF1 molecules accumulate on the 3'-untranslated region (3' UTR) of PTC-containing mRNAs and to an extent that is greater per unit 3' UTR length if the mRNA is an NMD target; (ii) UPF1 binding begins ≥35 nt downstream of the PTC; (iii) enhanced UPF1 binding to the 3' UTR of PTC-containing mRNA relative to its PTC-free counterpart depends on translation; and (iv) the presence of a 3' UTR exon-junction complex (EJC) further enhances UPF1 binding and/or affinity. Our data suggest that NMD involves UPF1 binding along a 3' UTR whether the 3' UTR contains an EJC. This binding explains how mRNAs without a 3' UTR EJC but with an abnormally long 3' UTR can be NMD targets, albeit not as efficiently as their counterparts that contain a 3' UTR EJC.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Kurosaki T,Maquat LE

doi

10.1073/pnas.1219908110

subject

Has Abstract

pub_date

2013-02-26 00:00:00

pages

3357-62

issue

9

eissn

0027-8424

issn

1091-6490

pii

1219908110

journal_volume

110

pub_type

杂志文章

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