METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved..
7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.
| Errataetall: |
CommentIn: Mol Cell. 2019 Jun 20;74(6):1105-1107. - PMID 31226274 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
|---|---|
| Enthalten in: |
Molecular cell - 74(2019), 6 vom: 20. Juni, Seite 1278-1290.e9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pandolfini, Luca [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.01.2020 Date Revised 14.02.2024 published: Print-Electronic CommentIn: Mol Cell. 2019 Jun 20;74(6):1105-1107. - PMID 31226274 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.molcel.2019.03.040 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM29650999X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM29650999X | ||
| 003 | DE-627 | ||
| 005 | 20240214232101.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.molcel.2019.03.040 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1292.xml |
| 035 | |a (DE-627)NLM29650999X | ||
| 035 | |a (NLM)31031083 | ||
| 035 | |a (PII)S1097-2765(19)30269-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pandolfini, Luca |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation |
| 264 | 1 | |c 2019 | |
| 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 13.01.2020 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Mol Cell. 2019 Jun 20;74(6):1105-1107. - PMID 31226274 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 7-methylguanosine | |
| 650 | 4 | |a G-quadruplexes | |
| 650 | 4 | |a METTL1 | |
| 650 | 4 | |a RNA methylation | |
| 650 | 4 | |a SAM-dependent methyltransferase | |
| 650 | 4 | |a cell migration | |
| 650 | 4 | |a high-throughput sequencing | |
| 650 | 4 | |a let-7 | |
| 650 | 4 | |a miRNA biogenesis | |
| 650 | 4 | |a microRNA | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a mirnlet7 microRNA, human |2 NLM | |
| 650 | 7 | |a Guanosine |2 NLM | |
| 650 | 7 | |a 12133JR80S |2 NLM | |
| 650 | 7 | |a 7-methylguanosine |2 NLM | |
| 650 | 7 | |a 2140-77-4 |2 NLM | |
| 650 | 7 | |a METTL1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 700 | 1 | |a Barbieri, Isaia |e verfasserin |4 aut | |
| 700 | 1 | |a Bannister, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Hendrick, Alan |e verfasserin |4 aut | |
| 700 | 1 | |a Andrews, Byron |e verfasserin |4 aut | |
| 700 | 1 | |a Webster, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Murat, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Mach, Pia |e verfasserin |4 aut | |
| 700 | 1 | |a Brandi, Rossella |e verfasserin |4 aut | |
| 700 | 1 | |a Robson, Samuel C |e verfasserin |4 aut | |
| 700 | 1 | |a Migliori, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Alendar, Andrej |e verfasserin |4 aut | |
| 700 | 1 | |a d'Onofrio, Mara |e verfasserin |4 aut | |
| 700 | 1 | |a Balasubramanian, Shankar |e verfasserin |4 aut | |
| 700 | 1 | |a Kouzarides, Tony |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cell |d 1998 |g 74(2019), 6 vom: 20. Juni, Seite 1278-1290.e9 |w (DE-627)NLM095914765 |x 1097-4164 |7 nnns |
| 773 | 1 | 8 | |g volume:74 |g year:2019 |g number:6 |g day:20 |g month:06 |g pages:1278-1290.e9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.molcel.2019.03.040 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 74 |j 2019 |e 6 |b 20 |c 06 |h 1278-1290.e9 | ||