Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module

Nucleic Acids Research
Todd R AlbrechtEric J Wagner

Abstract

Integrator (INT) is a transcriptional regulatory complex associated with RNA polymerase II that is required for the 3'-end processing of both UsnRNAs and enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic core of INT and are paralogues of the cleavage and polyadenylation specificity factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third protein called Symplekin, there is no paralog of Symplekin within INT raising the question of how INTS9/11 associate with the other INT subunits. Here, we have identified that INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually. Although INTS4 has no significant homology with Symplekin, it possesses N-terminal HEAT repeats similar to Symplekin but also contains a β-sheet rich C-terminal region, both of which are important to bind INTS9/11. We assess three functions of INT including UsnRNA 3'-end processing, maintenance of Cajal body structural integrity, and formation of histone locus bodies to conclude that INTS4/9/11 are the most critical of the INT subunits for UsnRNA biogenesis. Altogether, these results indicate that INTS4/9/11 compose a heterotrimeric complex that l...Continue Reading

References

Apr 1, 1992·The Journal of Cell Biology·M Carmo-FonsecaA I Lamond
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·M R Frey, A G Matera
Aug 1, 1996·The Journal of Cell Biology·B H KeonW W Franke
Feb 12, 2000·Molecular and Cellular Biology·Y Takagaki, J L Manley
Aug 8, 2001·The Journal of Cell Biology·M R Frey, A G Matera
Nov 7, 2002·Molecular Cell·Eric J Wagner, Mariano A Garcia-Blanco
Mar 17, 2004·The Journal of Cell Biology·Miroslav DundrTom Misteli
May 27, 2005·Biochemical Society Transactions·E J WagnerW F Marzluff
Oct 11, 2005·Cell·Zbigniew DominskiWilliam F Marzluff
Nov 23, 2006·Nature Methods·Daniel J FitzgeraldImre Berger
Apr 25, 2007·Critical Reviews in Biochemistry and Molecular Biology·Zbigniew Dominski
Jul 7, 2009·Journal of Molecular Biology·Sarah A KennedyMatthew R Redinbo
Dec 2, 2010·Molecular Biology of the Cell·Marc-David RueppDaniel Schümperli
Dec 21, 2010·Nature Cell Biology·Yuntao S MaoDavid L Spector
Jan 18, 2011·Nature Cell Biology·Sergey P Shevtsov, Miroslav Dundr
Sep 20, 2011·Molecular Cell·Demián CazallaJoan A Steitz
Jan 18, 2012·Journal of Cell Science·Hideaki TakataKei-ichi Shibahara
Jan 19, 2012·Molecular and Cellular Biology·Todd R Albrecht, Eric J Wagner
Mar 26, 2013·Biochemical and Biophysical Research Communications·Yuichiro OtaniTomoichiro Asano
Jun 12, 2013·Wiley Interdisciplinary Reviews. RNA·Natoya PeartEric J Wagner
Sep 24, 2013·PloS One·Ma'en ObeidatIan P Hall
Mar 5, 2014·Molecular and Cellular Biology·Kehui XiangJames L Manley
Sep 10, 2014·Molecular Cell·Alessandro GardiniRamin Shiekhattar
Apr 18, 2015·Trends in Biochemical Sciences·David Baillat, Eric J Wagner

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Citations

Oct 27, 2018·Wiley Interdisciplinary Reviews. RNA·Iain A SawyerMiroslav Dundr
Sep 19, 2019·Genes & Development·Deirdre C TatomerJeremy E Wilusz
Feb 23, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Deirdre C Tatomer, Jeremy E Wilusz
Aug 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Weili WangYunfeng Liu
Sep 15, 2020·Science Advances·Jasmine BarraJean-Christophe Marine
Oct 23, 2019·Journal of Cell Science·Cristina Moreno-CastroCarlos Suñé
Nov 25, 2020·The Journal of Biological Chemistry·Jian LiZigang Dong
Feb 7, 2021·Molecular Cell·Moritz M Pfleiderer, Wojciech P Galej
Jan 13, 2021·The Journal of Biological Chemistry·Jian LiZigang Dong
Sep 17, 2020·Science Advances·Jasmine BarraJean-Christophe Marine
May 1, 2021·International Journal of Molecular Sciences·Soeun HwangChang-Woo Lee
Dec 20, 2020·Current Opinion in Cell Biology·Nina KirsteinRamin Shiekhattar
Jun 14, 2021·Physical Chemistry Chemical Physics : PCCP·Tam D VoGregory M K Poon
Nov 4, 2021·Science Advances·Lucas Ferreira DasilvaRamin Shiekhattar

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Methods Mentioned

BETA
ChIP-seq
two-hybrid
PCR
transfections
transfection
gel filtration
co-immunoprecipitation
pulldown
two
two hybrid

Software Mentioned

NPAT
FLASH

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