The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons

RNA surveillance systems degrade aberrant RNAs that result from defective transcriptional termination, splicing, and polyadenylation. Defective RNAs in the nucleus are recognized by RNA-binding proteins and MTR4, and are degraded by the RNA exosome complex. Here, we detect aberrant RNAs in MTR4-depleted cells using long-read direct RNA sequencing and 3' sequencing. MTR4 destabilizes intronic polyadenylated transcripts generated by transcriptional read-through over one or more exons, termed 3' eXtended Transcripts (3XTs). MTR4 also associates with hnRNPK, which recognizes 3XTs with multiple exons. Moreover, the aberrant protein translated from KCTD13 3XT is a target of the hnRNPK-MTR4-RNA exosome pathway and forms aberrant condensates, which we name KCTD13 3eXtended Transcript-derived protein (KeXT) bodies. Our results suggest that RNA surveillance in human cells inhibits the formation of condensates of a defective polyadenylated transcript-derived protein.

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Publication Details

Journal
Nature Communications
Published
2024-10-17
DOI
https://doi.org/10.1038/s41467-024-51981-8
Primary Topic
RNA Research and Splicing
Type
article
Field-Weighted Citation Impact
0.00

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article

The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons

Nobuyoshi Akimitsu, Xinyue Gao, Michiaki Hamada, Chao Zeng et al.
Nature Communications
RNA Research and Splicing
article

The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons

Nobuyoshi Akimitsu, Xinyue Gao, Michiaki Hamada, Chao Zeng, Masahide Seki, Rena Onoguchi‐Mizutani, Yutaka Suzuki, Kenzui Taniue, Atsuko Nakanishi Ozeki, Yuki Shimoura, Han Han, Anzu Sugawara
article en

Abstract

RNA surveillance systems degrade aberrant RNAs that result from defective transcriptional termination, splicing, and polyadenylation. Defective RNAs in the nucleus are recognized by RNA-binding proteins and MTR4, and are degraded by the RNA exosome complex. Here, we detect aberrant RNAs in MTR4-depleted cells using long-read direct RNA sequencing and 3' sequencing. MTR4 destabilizes intronic polyadenylated transcripts generated by transcriptional read-through over one or more exons, termed 3' eXtended Transcripts (3XTs). MTR4 also associates with hnRNPK, which recognizes 3XTs with multiple exons. Moreover, the aberrant protein translated from KCTD13 3XT is a target of the hnRNPK-MTR4-RNA exosome pathway and forms aberrant condensates, which we name KCTD13 3eXtended Transcript-derived protein (KeXT) bodies. Our results suggest that RNA surveillance in human cells inhibits the formation of condensates of a defective polyadenylated transcript-derived protein.

Nature CommunicationsVol. 15(1)
Asahikawa Medical College Hospital (JP), Asahikawa Medical University (JP), Waseda University (JP), The University of Tokyo (JP)
Naito Foundation, Takeda Science Foundation, Aarhus Universitet, Novartis Foundation, Uehara Memorial Foundation, Japan Agency for Medical Research and Development, Ono Medical Research Foundation, NOVARTIS Foundation (Japan) for the Promotion of Science, Japan Society for the Promotion of Science
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RNA Research and Splicing
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