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4 results on '"mRNA decay pathway"'

1. Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions

Author

Ting-Wen Chen, Hsiao-Wei Liao, Michelle Noble, Jing-Yi Siao, Yu-Hsuan Cheng, Wei-Chung Chiang, Yi-Tzu Lo, and Chung-Te Chang

Subjects
mRNA decapping, DCP1 paralogs, DCP2, mRNA decay pathway, post-transcriptional regulation, Medicine, Science, Biology (General), QH301-705.5
Abstract

The mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.

Published
2024
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4. A specialised SKI complex assists the cytoplasmic RNA exosome in the absence of direct association with ribosomes

Author

Micheline Fromont-Racine, Abdelkader Namane, Antonia Doyen, Varun Khanna, Elodie Zhang, Alain Jacquier, Bernard Turcotte, Estelle Dacheux, Maïté Gomard, Génétique des Interactions macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), McGill University Health Center [Montreal] (MUHC), E. Z and E.D were supported by ANR‐14‐CE‐10‐0014‐01 and ANR‐17‐CE11‐0049‐01 grants from the Agence Nationale de la Recherche (ANR), respectively. This work was supported by ANR‐14‐CE‐10‐0014‐01 and ANR‐17‐CE11‐0049‐01 grants, the Pasteur Institute and the Centre National de la Recherche Scientifique. B.T. was supported by a grant from the Natural Sciences and Engineering Research Council of Canada., We thank colleagues mentioned in the text for their gifts of material. We are grateful to Julia Chamot‐Rooke and Mariette Matondo from the proteomic platform of the Pasteur Institute for the availability of the Orbitrap instrument and to Odile Sismeiro and Jean‐Yves Coppée from the Biomics pole of the Pasteur Institute for running the sequencing libraries on the Illumina machine. We thank the members of the laboratory, notably Cosmin Saveanu and Gwenael Breard for reading the manuscript, ANR-14-CE10-0014,CLEANMD,Mécanismes moléculaires et impact de la voie de dégradation des ARNm nonsense (NMD) sur le transcriptome eucaryote.(2014), ANR-17-CE11-0049,SKA,Caracterisation structurale et fonctionnelle d'un sous-complexe SKI chez Saccharomyces cerevisiae(2017), Institut Pasteur [Paris], Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral

Subjects
Untranslated region, Cytoplasm, Saccharomyces cerevisiae Proteins, animal structures, Exosome complex, RNA Stability, [SDV]Life Sciences [q-bio], Saccharomyces cerevisiae, Exosome, Ribosome, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, mRNA decay pathway, exosome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Ski complex, 3' Untranslated Regions, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Exosome Multienzyme Ribonuclease Complex, General Immunology and Microbiology, biology, General Neuroscience, RNA, RNA, Fungal, SKI complex, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Articles, biology.organism_classification, musculoskeletal system, Cell biology, ribosome, RNA, Long Noncoding, 5' Untranslated Regions, Ribosomes, human activities, 030217 neurology & neurosurgery
Abstract

International audience; The Ski2-Ski3-Ski8 (SKI) complex assists the RNA exosome during the 3' to 5' degradation of cytoplasmic transcripts. Previous reports showed that the SKI complex is involved in the 3' to 5' degradation of mRNAs, including 3' untranslated regions (UTRs) and devoid of ribosomes. Paradoxically, we recently showed that the SKI complex directly interacts with ribosomes during the co-translational mRNA decay and that this interaction is necessary for its RNA degradation promoting activity. Here, we characterised a new SKI-associated factor, Ska1, that associates with a subpopulation of the SKI complex. We showed that Ska1 is specifically involved in the degradation of long 3'UTR-containing mRNAs, poorly translated mRNAs as well as other RNA regions not associated with ribosomes, such as cytoplasmic lncRNAs. We further show that the overexpression of SKA1 antagonises the SKI-ribosome association. We propose that the Ska1-SKI complex assists the cytoplasmic exosome in the absence of direct association of the SKI complex with ribosomes.

Published
2019
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