Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research..
The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3'UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation correlated with translation termination. While NSUN6 was dispensable for mouse embryonic development, it was down-regulated in human tumours and high expression of NSUN6 indicated better patient outcome of certain cancer types. In summary, our study identifies NSUN6 as a methyltransferase targeting mRNA, potentially as part of a quality control mechanism involved in translation termination fidelity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
|---|---|
| Enthalten in: |
Nucleic acids research - 49(2021), 2 vom: 25. Jan., Seite 1006-1022 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Selmi, Tommaso [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3' Untranslated Regions |
|---|
| Anmerkungen: |
Date Completed 03.02.2021 Date Revised 10.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/nar/gkaa1193 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM318959844 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM318959844 | ||
| 003 | DE-627 | ||
| 005 | 20240210232324.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/nar/gkaa1193 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1286.xml |
| 035 | |a (DE-627)NLM318959844 | ||
| 035 | |a (NLM)33330931 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Selmi, Tommaso |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.02.2021 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. | ||
| 520 | |a The highly abundant N6-methyladenosine (m6A) RNA modification affects most aspects of mRNA function, yet the precise function of the rarer 5-methylcytidine (m5C) remains largely unknown. Here, we map m5C in the human transcriptome using methylation-dependent individual-nucleotide resolution cross-linking and immunoprecipitation (miCLIP) combined with RNA bisulfite sequencing. We identify NSUN6 as a methyltransferase with strong substrate specificity towards mRNA. NSUN6 primarily targeted three prime untranslated regions (3'UTR) at the consensus sequence motif CTCCA, located in loops of hairpin structures. Knockout and rescue experiments revealed enhanced mRNA and translation levels when NSUN6-targeted mRNAs were methylated. Ribosome profiling further demonstrated that NSUN6-specific methylation correlated with translation termination. While NSUN6 was dispensable for mouse embryonic development, it was down-regulated in human tumours and high expression of NSUN6 indicated better patient outcome of certain cancer types. In summary, our study identifies NSUN6 as a methyltransferase targeting mRNA, potentially as part of a quality control mechanism involved in translation termination fidelity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a 3' Untranslated Regions |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Cytidine |2 NLM | |
| 650 | 7 | |a 5CSZ8459RP |2 NLM | |
| 650 | 7 | |a NSUN6 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a tRNA Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a 5-methylcytidine |2 NLM | |
| 650 | 7 | |a TL9PB228DC |2 NLM | |
| 700 | 1 | |a Hussain, Shobbir |e verfasserin |4 aut | |
| 700 | 1 | |a Dietmann, Sabine |e verfasserin |4 aut | |
| 700 | 1 | |a Heiß, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Borland, Kayla |e verfasserin |4 aut | |
| 700 | 1 | |a Flad, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Carter, Jean-Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Dennison, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ya-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Kellner, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Bornelöv, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Frye, Michaela |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nucleic acids research |d 1974 |g 49(2021), 2 vom: 25. Jan., Seite 1006-1022 |w (DE-627)NLM000063398 |x 1362-4962 |7 nnns |
| 773 | 1 | 8 | |g volume:49 |g year:2021 |g number:2 |g day:25 |g month:01 |g pages:1006-1022 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/nar/gkaa1193 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 49 |j 2021 |e 2 |b 25 |c 01 |h 1006-1022 | ||