TY - JOUR
T1 - The Integrator complex at the crossroad of coding and noncoding RNA
AU - Kirstein, Nina
AU - Gomes Dos Santos, Helena
AU - Blumenthal, Ezra
AU - Shiekhattar, Ramin
N1 - Funding Information:
The authors thank the Shiekhattar laboratory members for discussions and helpful comments. RS is supported by the University of Miami Miller School of Medicine , Sylvester Comprehensive Cancer Center and grants R01 GM078455 and GM105754 , and DP1 CA228041 from the National Institute of Health , and the National Cancer Institute of the National Institutes of Health Award Number P30CA240139.
Funding Information:
The authors thank the Shiekhattar laboratory members for discussions and helpful comments. RS is supported by the University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center and grants R01 GM078455 and GM105754, and DP1 CA228041 from the National Institute of Health, and the National Cancer Institute of the National Institutes of Health Award Number P30CA240139.
Publisher Copyright:
© 2020 The Authors
PY - 2021/6
Y1 - 2021/6
N2 - Genomic transcription is fundamental to all organisms. In metazoans, the Integrator complex is required for endonucleolytic processing of noncoding RNAs, regulation of RNA polymerase II pause–release, and premature transcription attenuation at coding genes. Recent insights into the structural composition and evolution of Integrator subunits have informed our understanding of its biochemical functionality. Moreover, studies in multiple model organisms point to an essential function of Integrator in signaling response and cellular development, highlighting a key role in neuronal differentiation. Indeed, alterations in Integrator complex subunits have been identified in patients with neurodevelopmental diseases and cancer. Taken together, we propose that Integrator is a central regulator of transcriptional processes and that its evolution reflects genomic complexity in regulatory elements and chromatin architecture.
AB - Genomic transcription is fundamental to all organisms. In metazoans, the Integrator complex is required for endonucleolytic processing of noncoding RNAs, regulation of RNA polymerase II pause–release, and premature transcription attenuation at coding genes. Recent insights into the structural composition and evolution of Integrator subunits have informed our understanding of its biochemical functionality. Moreover, studies in multiple model organisms point to an essential function of Integrator in signaling response and cellular development, highlighting a key role in neuronal differentiation. Indeed, alterations in Integrator complex subunits have been identified in patients with neurodevelopmental diseases and cancer. Taken together, we propose that Integrator is a central regulator of transcriptional processes and that its evolution reflects genomic complexity in regulatory elements and chromatin architecture.
KW - Cancer
KW - INTS evolution
KW - Integrator complex
KW - Neurodevelopmental diseases
KW - RNA processing
KW - Transcription regulation
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U2 - 10.1016/j.ceb.2020.11.003
DO - 10.1016/j.ceb.2020.11.003
M3 - Review article
C2 - 33340967
AN - SCOPUS:85097788076
VL - 70
SP - 37
EP - 43
JO - Current Opinion in Cell Biology
JF - Current Opinion in Cell Biology
SN - 0955-0674
ER -