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Short poly(A) tails are protected from deadenylation by the LARP1-PABP complex

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Title
Short poly(A) tails are protected from deadenylation by the LARP1-PABP complex
Author(s)
Joha Park; Myeonghwan Kim; Hyerim Yi; Kyungmin Baeg; Yongkuk Choi; Young-suk Lee; Jaechul Lim; V. Narry Kim
Publication Date
2023-02
Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY, v.30, no.3, pp.330 - 338
Publisher
NATURE PORTFOLIO
Abstract
Deadenylation generally constitutes the first and pivotal step in eukaryotic messenger RNA decay. Despite its importance in posttranscriptional regulations, the kinetics of deadenylation and its regulation remain largely unexplored. Here we identify La ribonucleoprotein 1, translational regulator (LARP1) as a general decelerator of deadenylation, which acts mainly in the 30-60-nucleotide (nt) poly(A) length window. We measured the steady-state and pulse-chased distribution of poly(A)-tail length, and found that deadenylation slows down in the 30-60-nt range. LARP1 associates preferentially with short tails and its depletion results in accelerated deadenylation specifically in the 30-60-nt range. Consistently, LARP1 knockdown leads to a global reduction of messenger RNA abundance. LARP1 interferes with the CCR4-NOT-mediated deadenylation in vitro by forming a ternary complex with poly(A)-binding protein (PABP) and poly(A). Together, our work reveals a dynamic nature of deadenylation kinetics and a role of LARP1 as a poly(A) length-specific barricade that creates a threshold for deadenylation.
URI
https://pr.ibs.re.kr/handle/8788114/13079
DOI
10.1038/s41594-023-00930-y
ISSN
1545-9993
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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