Inhibition of cytoplasmic cap methylation identifies 5′ TOP mRNAs as recapping targets and reveals recapping sites downstream of native 5′ ends
| العنوان: | Inhibition of cytoplasmic cap methylation identifies 5′ TOP mRNAs as recapping targets and reveals recapping sites downstream of native 5′ ends |
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| المؤلفون: | Jackson B. Trotman, Ralf Bundschuh, Daniel del Valle Morales, Daniel R. Schoenberg |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | RNA Caps, Cytoplasm, Polyadenylation, AcademicSubjects/SCI00010, Regulatory Sequences, Ribonucleic Acid, Biology, RNA 5' Terminal Oligopyrimidine Sequence, Methylation, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Cell Line, Tumor, Gene expression, RNA and RNA-protein complexes, Genetics, Humans, RNA, Messenger, 030304 developmental biology, 0303 health sciences, Messenger RNA, RNA-Binding Proteins, Cell biology, DNA-Binding Proteins, Gene Expression Regulation, RNA splicing, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | Cap homeostasis is the cyclical process of decapping and recapping that maintains the translation and stability of a subset of the transcriptome. Previous work showed levels of some recapping targets decline following transient expression of an inactive form of RNMT (ΔN-RNMT), likely due to degradation of mRNAs with improperly methylated caps. The current study examined transcriptome-wide changes following inhibition of cytoplasmic cap methylation. This identified mRNAs with 5′-terminal oligopyrimidine (TOP) sequences as the largest single class of recapping targets. Cap end mapping of several TOP mRNAs identified recapping events at native 5′ ends and downstream of the TOP sequence of EIF3K and EIF3D. This provides the first direct evidence for downstream recapping. Inhibition of cytoplasmic cap methylation was also associated with mRNA abundance increases for a number of transcription, splicing, and 3′ processing factors. Previous work suggested a role for alternative polyadenylation in target selection, but this proved not to be the case. However, inhibition of cytoplasmic cap methylation resulted in a shift of upstream polyadenylation sites to annotated 3′ ends. Together, these results solidify cap homeostasis as a fundamental process of gene expression control and show cytoplasmic recapping can impact regulatory elements present at the ends of mRNA molecules. |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7e2a7649992cf74a3da34c21c5e94c7a https://doi.org/10.1093/nar/gkaa046 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7e2a7649992cf74a3da34c21c5e94c7a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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