Disruption of the Caenorhabditis elegans Integrator complex triggers a non-conventional transcriptional mechanism beyond snRNA genes

PLoS Genetics
Eva Gómez-OrteJuan Cabello

Abstract

Gene expression is generally regulated by recruitment of transcription factors and RNA polymerase II (RNAP II) to specific sequences in the gene promoter region. The Integrator complex mediates processing of small nuclear RNAs (snRNAs) as well as the initiation and release of paused RNAP II at specific genes in response to growth factors. Here we show that in C. elegans, disruption of the Integrator complex leads to transcription of genes located downstream of the snRNA loci via a non-conventional transcription mechanism based on the lack of processing of the snRNAs. RNAP II read-through generates long chimeric RNAs containing snRNA, the intergenic region and the mature mRNA of the downstream gene located in sense. These chimeric sn-mRNAs remain as untranslated long non-coding RNAs, in the case of U1- and U2-derived sn-mRNAs, but can be translated to proteins in the case of SL-derived sn-mRNAs. The transcriptional effect caused by disruption of the Integrator complex is not restricted to genes located downstream of the snRNA loci but also affects key regulators of signal transduction such as kinases and phosphatases. Our findings highlight that these transcriptional alterations may be behind the correlation between mutations in...Continue Reading

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Citations

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
Dec 20, 2020·Current Opinion in Cell Biology·Nina KirsteinRamin Shiekhattar
Sep 23, 2021·Nucleic Acids Research·Jana Wiedermannová, Libor Krásný

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Datasets Mentioned

BETA
GSE111083

Methods Mentioned

BETA
transgenic
Immunoprecipitation
co-immunoprecipitation
PCR
electrophoresis
RNAseq
Illumina sequencing
transfection
RNA seq
affinity purification

Software Mentioned

Qualimap2
Pathview
ImageJ
Trimmomatic
Upset
Tophat2
enrichGO
ReactomePA
SARTools
enrichKEGG

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