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m 6 A modification of HSATIII lncRNAs regulates temperature‐dependent splicing
Author(s) -
Ninomiya Kensuke,
Iwakiri Junichi,
Aly Mahmoud Khamis,
Sakaguchi Yuriko,
Adachi Shungo,
Natsume Tohru,
Terai Goro,
Asai Kiyoshi,
Suzuki Tsutomu,
Hirose Tetsuro
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2021107976
Subject(s) - biology , rna splicing , intron , nucleoplasm , ribonucleoprotein , splicing factor , rna binding protein , sr protein , microbiology and biotechnology , exonic splicing enhancer , rna , genetics , gene , nucleolus , cytoplasm
Nuclear stress bodies (nSBs) are nuclear membraneless organelles formed around stress‐inducible HSATIII architectural long noncoding RNAs (lncRNAs). nSBs repress splicing of hundreds of introns during thermal stress recovery, which are partly regulated by CLK1 kinase phosphorylation of temperature‐dependent Ser/Arg‐rich splicing factors (SRSFs). Here, we report a distinct mechanism for this splicing repression through protein sequestration by nSBs. Comprehensive identification of RNA‐binding proteins revealed HSATIII association with proteins related to N 6 ‐methyladenosine (m 6 A) RNA modification. 11% of the first adenosine in the repetitive HSATIII sequence were m 6 A‐modified. nSBs sequester the m 6 A writer complex to methylate HSATIII, leading to subsequent sequestration of the nuclear m 6 A reader, YTHDC1. Sequestration of these factors from the nucleoplasm represses m 6 A modification of pre‐mRNAs, leading to repression of m 6 A‐dependent splicing during stress recovery phase. Thus, nSBs serve as a common platform for regulation of temperature‐dependent splicing through dual mechanisms employing two distinct ribonucleoprotein modules with partially m 6 A‐modified architectural lncRNAs.