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LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy

LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding pro...

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Autores principales: Hwang, Hyun Jung, Ha, Hongseok, Lee, Ban Seok, Kim, Bong Heon, Song, Hyun Kyu, Kim, Yoon Ki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931120/
https://www.ncbi.nlm.nih.gov/pubmed/35302060
http://dx.doi.org/10.1038/s41467-022-29139-1
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author Hwang, Hyun Jung
Ha, Hongseok
Lee, Ban Seok
Kim, Bong Heon
Song, Hyun Kyu
Kim, Yoon Ki
author_facet Hwang, Hyun Jung
Ha, Hongseok
Lee, Ban Seok
Kim, Bong Heon
Song, Hyun Kyu
Kim, Yoon Ki
author_sort Hwang, Hyun Jung
collection PubMed
description LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding protein that directly binds to mRNAs with a preference for a consensus AAUAAA motif corresponding to a polyadenylation sequence. Autophagic activation promotes an association between LC3B and target mRNAs and triggers rapid degradation of target mRNAs in a CCR4-NOT–dependent manner before autolysosome formation. Furthermore, our transcriptome-wide analysis reveals that PRMT1 mRNA, which encodes a negative regulator of autophagy, is one of the major substrates. Rapid degradation of PRMT1 mRNA by LC3B facilitates autophagy. Collectively, we demonstrate that LC3B acts as an RNA-binding protein and an mRNA decay factor necessary for efficient autophagy.
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spelling pubmed-89311202022-04-01 LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy Hwang, Hyun Jung Ha, Hongseok Lee, Ban Seok Kim, Bong Heon Song, Hyun Kyu Kim, Yoon Ki Nat Commun Article LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding protein that directly binds to mRNAs with a preference for a consensus AAUAAA motif corresponding to a polyadenylation sequence. Autophagic activation promotes an association between LC3B and target mRNAs and triggers rapid degradation of target mRNAs in a CCR4-NOT–dependent manner before autolysosome formation. Furthermore, our transcriptome-wide analysis reveals that PRMT1 mRNA, which encodes a negative regulator of autophagy, is one of the major substrates. Rapid degradation of PRMT1 mRNA by LC3B facilitates autophagy. Collectively, we demonstrate that LC3B acts as an RNA-binding protein and an mRNA decay factor necessary for efficient autophagy. Nature Publishing Group UK 2022-03-17 /pmc/articles/PMC8931120/ /pubmed/35302060 http://dx.doi.org/10.1038/s41467-022-29139-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hwang, Hyun Jung
Ha, Hongseok
Lee, Ban Seok
Kim, Bong Heon
Song, Hyun Kyu
Kim, Yoon Ki
LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title_full LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title_fullStr LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title_full_unstemmed LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title_short LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
title_sort lc3b is an rna-binding protein to trigger rapid mrna degradation during autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931120/
https://www.ncbi.nlm.nih.gov/pubmed/35302060
http://dx.doi.org/10.1038/s41467-022-29139-1
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