Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes

Nature Communications
Bernd StadelmayerMonsef Benkirane

Abstract

RNA polymerase II (RNAPII) pausing/termination shortly after initiation is a hallmark of gene regulation. Here, we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both human immunodeficiency virus type 1 promoter and genome-wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated INTScom subunits. Interestingly, in addition to controlling RNAPII pause-release INTS11 catalytic subunit of the INTScom is required for RNAPII processivity. Finally, INTScom target genes are enriched in human immunodeficiency virus type 1 transactivation response element/NELF binding element and in a 3' box sequence required for small nuclear RNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pause-release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle.

References

Nov 12, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Adam Scheidegger, Sergei Nechaev
Sep 25, 2015·Transcription·Clélia LaitemShona Murphy
Aug 27, 2015·Nature·Fan LaiRamin Shiekhattar
Apr 18, 2015·Trends in Biochemical Sciences·David Baillat, Eric J Wagner
Jun 11, 2016·ELife·Seychelle M VosPatrick Cramer
Jul 20, 2016·Biochimica Et Biophysica Acta·Monica Rienzo, Amelia Casamassimi
Oct 22, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Iain A SawyerMiroslav Dundr
May 5, 2017·International Journal of Molecular Sciences·Antonio FedericoAmelia Casamassimi
Dec 1, 2017·Nature Reviews. Molecular Cell Biology·Ivan MarazziErnesto Guccione
Aug 8, 2017·Chemistry, an Asian Journal·Lilu Zhang, Eric Meggers
Mar 11, 2018·Nature Communications·Marina E BorisovaPetra Beli
Jun 16, 2017·Open Biology·Joana Guiro, Shona Murphy
Sep 19, 2019·Genes & Development·Deirdre C TatomerJeremy E Wilusz
Jan 19, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lihua ShiKathleen E Sullivan
Feb 23, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Deirdre C Tatomer, Jeremy E Wilusz
Feb 7, 2019·Nature Structural & Molecular Biology·Fernando Aprile-GarciaRitwick Sawarkar
Jun 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Liming HouBrian David Dynlacht
Aug 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Weili WangYunfeng Liu
Feb 10, 2019·Scientific Reports·M P RubtsovaO A Dontsova
Mar 13, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shinichi MachidaMonsef Benkirane
Apr 4, 2020·Nature Reviews. Molecular Cell Biology·Caitlin M Roake, Steven E Artandi
Sep 8, 2016·The Journal of Biological Chemistry·Melissa RestoBrian A Lewis
Apr 13, 2020·Molecular Cancer·Yuan TanFaqing Tang
Apr 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yixuan WuLiang Tong

Citations

Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Jan 10, 2004·Methods in Enzymology·Yoshihiro Nakatani, Vasily Ogryzko
May 20, 2005·Current Opinion in Cell Biology·Stephen Buratowski
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Aug 4, 2006·Molecular Cell·B Matija Peterlin, David H Price
Jun 3, 2008·Current Opinion in Cell Biology·Vanessa BrèsKatherine A Jones
Jul 18, 2008·Biochemical Society Transactions·Sylvain EgloffShona Murphy
Jul 17, 2009·The Journal of Biological Chemistry·Yongjiang LiWeidong Wang
Aug 18, 2009·Molecular Cell·Jun HuangJunjie Chen
Sep 30, 2009·The Journal of Cell Biology·Jeffrey R SkaarMichele Pagano
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anamika Missra, David S Gilmour
Jul 28, 2010·Biochemical Society Transactions·Jiandong Chen, Eric J Wagner
Jul 28, 2012·Nature Protocols·Morgane Thomas-ChollierJacques van Helden
Sep 18, 2012·Biochimica Et Biophysica Acta·Martin HeidemannDirk Eick
Sep 19, 2012·Nature Reviews. Genetics·Karen Adelman, John T Lis
Dec 4, 2012·Biochimica Et Biophysica Acta·Yuki YamaguchiHiroshi Handa
May 30, 2013·Transcription·Xavier ContrerasRosemary Kiernan
Aug 21, 2013·PLoS Computational Biology·Michael LawrenceVincent J Carey
Aug 30, 2013·Journal of Cell Science·Feng ZhangXiaochun Yu
Sep 21, 2013·Annual Review of Genetics·Hojoong Kwak, John T Lis
Jan 24, 2014·PLoS Genetics·John M PaganoJohn T Lis
Sep 10, 2014·Molecular Cell·Alessandro GardiniRamin Shiekhattar

Related Concepts

RNA Polymerase II
Small Nuclear RNA
Elongation Factor
Small Nuclear RNA Location
Trans-Activation, Genetic
Transcription Initiation
Promoter
Integrator, veterinary brand name drug
HIV Infections
Gene Expression

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.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

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.