Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia.

Nature
Shih-Han LeeChristine Mayr

Abstract

DNA mutations are known cancer drivers. Here we investigated whether mRNA events that are upregulated in cancer can functionally mimic the outcome of genetic alterations. RNA sequencing or 3'-end sequencing techniques were applied to normal and malignant B cells from 59 patients with chronic lymphocytic leukaemia (CLL)1-3. We discovered widespread upregulation of truncated mRNAs and proteins in primary CLL cells that were not generated by genetic alterations but instead occurred by intronic polyadenylation. Truncated mRNAs caused by intronic polyadenylation were recurrent (n = 330) and predominantly affected genes with tumour-suppressive functions. The truncated proteins generated by intronic polyadenylation often lack the tumour-suppressive functions of the corresponding full-length proteins (such as DICER and FOXN3), and several even acted in an oncogenic manner (such as CARD11, MGA and CHST11). In CLL, the inactivation of tumour-suppressor genes by aberrant mRNA processing is substantially more prevalent than the functional loss of such genes through genetic events. We further identified new candidate tumour-suppressor genes that are inactivated by intronic polyadenylation in leukaemia and by truncating DNA mutations in soli...Continue Reading

References

Jan 5, 2002·The Journal of Biological Chemistry·Julie MillandMauro S Sandrin
Jan 19, 2002·Genes & Development·Bing RenBrian David Dynlacht
Jun 1, 2002·Leukemia·S StilgenbauerUNKNOWN German CLL Study Group (GCLLSG). Chronic lymphocytic leukemia
Apr 18, 2003·Current Biology : CB·Michael T VeemanRandall T Moon
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zirong LiBing Ren
Jan 14, 2005·Nucleic Acids Research·Bin TianCarol S Lutz
Nov 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Karen I ZellerChia-Lin Wei
Mar 8, 2008·Science·Georg LenzLouis M Staudt
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Richard G JennerGraham M Lord
Dec 3, 2010·The Journal of Biological Chemistry·Satomi NadanakaHiroshi Kitagawa
Aug 13, 2011·Nature·Alice H BergerPier Paolo Pandolfi
Jun 23, 2012·Genome Research·Simon AndersWolfgang Huber
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Jan 10, 2014·Molecular Biology of the Cell·Geneviève HuotGerardo Ferbeyre
Apr 22, 2015·Nature·Binyamin D Berkovits, Christine Mayr
Oct 16, 2015·Nature·Dan A LandauCatherine J Wu
Mar 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Young-Kook KimV Narry Kim
Jun 11, 2016·Nature Reviews. Cancer·Heidi DvingeRobert K Bradley
Jun 14, 2016·Cell Reports·Santhosh KaranthAmnon Schlegel
May 2, 2018·Nature Communications·Irtisha SinghChristina S Leslie

❮ Previous
Next ❯

Citations

Sep 11, 2019·Nucleic Acids Research·Eldad David Shulman, Ran Elkon
Sep 26, 2019·Physiological Reports·Santhosh KaranthAmnon Schlegel
Sep 6, 2018·Cold Spring Harbor Perspectives in Biology·Christine Mayr
Apr 11, 2019·Blood·Daniel J HodsonMartin Turner
Jul 4, 2019·Nature Reviews. Genetics·Andreas J Gruber, Mihaela Zavolan
Sep 27, 2019·Nature Reviews. Drug Discovery·Joana DesterroMaria Carmo-Fonseca
Dec 13, 2019·Nature Communications·Yifan WangNeil Johnson
May 27, 2020·Experimental & Molecular Medicine·Seung Hyuk ChoiKatherine A Jones
Jan 5, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Christine Mayr
Sep 26, 2020·Nucleic Acids Research·Federico MariniSven Danckwardt
Sep 29, 2020·Nucleic Acids Research·Jackson B TrotmanJ Mauro Calabrese
Oct 26, 2018·Nucleic Acids Research·Kathryn L BlackAndrei Thomas-Tikhonenko
Sep 23, 2018·Nature Reviews. Cancer·Sarah Seton-Rogers
Jun 20, 2019·Frontiers in Oncology·Xiangyi KongYi Fang
Nov 15, 2019·Nucleic Acids Research·Geoffray MonteuuisJohn E J Rasko
May 16, 2020·Human Molecular Genetics·Kiel T Tietz, Scott M Dehm
Apr 30, 2020·Experimental & Molecular Medicine·Hee Doo Yang, Suk Woo Nam
Jan 9, 2020·Nature Communications·Jung-Min OhGideon Dreyfuss
May 4, 2020·Cancer Metastasis Reviews·Ayse Elif Erson-Bensan
Apr 8, 2020·Oncotarget·Souhila AbdelfettahDominique Leprince
Jun 5, 2020·Science Advances·Zheng FanRicky W Johnstone
Aug 1, 2019·Nature Reviews. Immunology·Luke FrankiwGuideng Li
Aug 11, 2020·International Journal of Endocrinology·Xiaohui TongTongsheng Wang
Nov 30, 2018·Nature Reviews. Clinical Oncology·Bing ZhangAmanda G Paulovich
Sep 4, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yen-Chun LiuJulia T Geyer
Aug 22, 2020·Journal of Lipid and Atherosclerosis·Hsin-Sung Yeh, Jeongsik Yong
Oct 22, 2020·Nature Reviews. Cancer·Gregory J Goodall, Vihandha O Wickramasinghe
Oct 16, 2019·Cancer Discovery·Esther A ObengOmar Abdel-Wahab
May 10, 2020·Computational and Structural Biotechnology Journal·Congting YeQingshun Q Li
Oct 14, 2020·Trends in Genetics : TIG·Cécilia StudniarekShona Murphy
Oct 25, 2019·Genes & Diseases·Fuwen YuanQianben Wang
Feb 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yi ZhangPengyuan Liu
Jan 10, 2021·Cancers·Irina A Elcheva, Vladimir S Spiegelman
Mar 4, 2021·Trends in Biochemical Sciences·Martin DutertreStéphan Vagner
Feb 24, 2021·Trends in Cancer·Swati VenkatMichael E Feigin
Sep 13, 2020·Science Advances·Zheng FanRicky W Johnstone

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Datasets Mentioned

BETA
BC136659

Methods Mentioned

BETA
3′-seq
RNA-seq
FCS
PCRs
cleavage assay
transfection
FACS
PCR
exome sequencing

Software Mentioned

FlowJo
TUSON Explorer
DESeq

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