mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis.

Nature
Junho ChoeRichard I Gregory

Abstract

N6-methyladenosine (m6A) modification of mRNA is emerging as an important regulator of gene expression that affects different developmental and biological processes, and altered m6A homeostasis is linked to cancer1-5. m6A modification is catalysed by METTL3 and enriched in the 3' untranslated region of a large subset of mRNAs at sites close to the stop codon5. METTL3 can promote translation but the mechanism and relevance of this process remain unknown1. Here we show that METTL3 enhances translation only when tethered to reporter mRNA at sites close to the stop codon, supporting a mechanism of mRNA looping for ribosome recycling and translational control. Electron microscopy reveals the topology of individual polyribosomes with single METTL3 foci in close proximity to 5' cap-binding proteins. We identify a direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h). METTL3 promotes translation of a large subset of oncogenic mRNAs-including bromodomain-containing protein 4-that is also m6A-modified in human primary lung tumours. The METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformatio...Continue Reading

References

Aug 14, 1998·Molecular Cell·S E WellsA B Sachs
Jul 26, 2002·The Journal of Biological Chemistry·Andrew M BormanKatherine M Kean
Jun 12, 2008·The Journal of Biological Chemistry·Lili ZhangJohn W B Hershey
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Dec 10, 2013·Nature Chemical Biology·Jianzhao LiuChuan He
Apr 10, 2014·Nature Reviews. Molecular Cell Biology·Kate D Meyer, Samie R Jaffrey
Sep 23, 2014·Nature Chemical Biology·Chao XuJinrong Min
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Dec 3, 2014·Biochimica Et Biophysica Acta·John W B Hershey
Dec 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shihao ShenYi Xing
May 8, 2015·Nature Protocols·Lawrence A KelleyMichael J E Sternberg
Sep 8, 2015·Nature·Amedee des GeorgesYaser Hashem
Dec 26, 2015·Nucleic Acids Research·Antonio ColapricoHoutan Noushmehr
Apr 28, 2016·Molecular Cell·Shuibin LinRichard I Gregory
Nov 25, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mengnuo ChenChun-Ming Wong

❮ Previous
Next ❯

Citations

May 31, 2019·Nucleic Acids Research·Qi Liu, Richard I Gregory
Sep 15, 2019·Nature Reviews. Molecular Cell Biology·Sara ZaccaraSamie R Jaffrey
Jul 10, 2019·Annual Review of Virology·Graham D WilliamsStacy M Horner
Apr 11, 2019·Blood·Daniel J HodsonMartin Turner
Jul 25, 2019·Journal of Molecular Cell Biology·Marlene ReichelDorothee Staiger
Mar 4, 2020·International Journal of Molecular Sciences·Olga M AlekhinaKonstantin S Vassilenko
May 3, 2019·Nature Cell Biology·Sylvain Delaunay, Michaela Frye
Oct 18, 2019·Nature Protocols·Shuibin LinRichard I Gregory
Apr 5, 2020·Molecular Cancer·Chaoqin ShenJie Hong
Aug 26, 2020·Molecular Biotechnology·R Karthiya, Piyush Khandelia
Sep 9, 2020·Open Biology·Wenxiu RuHong Chen
Oct 5, 2019·Nature Structural & Molecular Biology·Konstantinos TzelepisTony Kouzarides
Aug 1, 2019·Nature Communications·G Guy BushkinGerald R Fink
Apr 5, 2020·Cancers·Zhen Dong, Hongjuan Cui
May 24, 2020·Nature Communications·Zihan LiHongsheng Wang
Jul 21, 2020·Wiley Interdisciplinary Reviews. RNA·David Garcias Morales, José L Reyes
Sep 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiaobin GuoZhihua Liu
Oct 13, 2018·Nature Reviews. Cancer·Ulrike Harjes
Nov 24, 2019·Journal of Hematology & Oncology·Shuai MaZhenqiang Sun
Apr 3, 2020·RNA Biology·Andrea J BermanSarah P Blagden
Jun 10, 2020·Molecular Cancer·Zijian ZhouHaiwei Yang
Jul 9, 2020·Biomolecules·Daria Lavysh, Gabriele Neu-Yilik
May 14, 2020·Molecular Cancer·Tianyi WangShaoqing Ju
Aug 8, 2020·Cancer Cell International·Guanqun YangNan Zhang
Apr 23, 2020·International Journal of Molecular Sciences·Ruben Mercado SantosWen Cai Zhang
Jan 2, 2019·International Journal of Molecular Sciences·Sylvain de Breyne, Théophile Ohlmann
Apr 27, 2019·Frontiers in Oncology·Zaira IannielloAlessandro Fatica
Dec 11, 2019·International Journal of Molecular Sciences·Wen Cai Zhang
Jan 11, 2020·Frontiers in Oncology·Wenhui ZhengMing Gu
Jan 11, 2020·Frontiers in Oncology·Sihui YuSufang Wu

❮ Previous
Next ❯

Methods Mentioned

BETA
electron microscopy
pull-down
proximity ligation assay
immunoprecipitation
PCR
RNA-seq
PAR-CLIP
Co-immunoprecipitation
xenografts
transfection

Software Mentioned

Integrative viewer
Tophat2
GENCODE
R package TCGAbiolinks
rMATS
HTSeq
AMT Capture engine

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.