The Integrator complex regulates microRNA abundance through RISC loading
MicroRNA (miRNA) homeostasis is crucial for the posttranscriptional regulation of their target genes during development and in disease states. miRNAs are derived from primary transcripts and are processed from a hairpin precursor intermediary to a mature 22-nucleotide duplex RNA. Loading of the dupl...
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| Veröffentlicht in: | Science advances 2023-02, Vol.9 (6), p.eadf0597 |
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| creator | Kirstein, Nina Dokaneheifard, Sadat Cingaram, Pradeep Reddy Valencia, Monica Guiselle Beckedorff, Felipe Gomes Dos Santos, Helena Blumenthal, Ezra Tayari, Mina Masoumeh Gaidosh, Gabriel Stephen Shiekhattar, Ramin |
| description | MicroRNA (miRNA) homeostasis is crucial for the posttranscriptional regulation of their target genes during development and in disease states. miRNAs are derived from primary transcripts and are processed from a hairpin precursor intermediary to a mature 22-nucleotide duplex RNA. Loading of the duplex into the Argonaute (AGO) protein family is pivotal to miRNA abundance and its posttranscriptional function. The Integrator complex plays a key role in protein coding and noncoding RNA maturation, RNA polymerase II pause-release, and premature transcriptional termination. Here, we report that loss of Integrator results in global destabilization of mature miRNAs. Enhanced ultraviolet cross-linking and immunoprecipitation of Integrator uncovered an association with duplex miRNAs before their loading onto AGOs. Tracing miRNA fate from biogenesis to stabilization by incorporating 4-thiouridine in nascent transcripts pinpointed a critical role for Integrator in miRNA assembly into AGOs. |
| doi_str_mv | 10.1126/sciadv.adf0597 |
| format | Article |
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Loading of the duplex into the Argonaute (AGO) protein family is pivotal to miRNA abundance and its posttranscriptional function. The Integrator complex plays a key role in protein coding and noncoding RNA maturation, RNA polymerase II pause-release, and premature transcriptional termination. Here, we report that loss of Integrator results in global destabilization of mature miRNAs. Enhanced ultraviolet cross-linking and immunoprecipitation of Integrator uncovered an association with duplex miRNAs before their loading onto AGOs. Tracing miRNA fate from biogenesis to stabilization by incorporating 4-thiouridine in nascent transcripts pinpointed a critical role for Integrator in miRNA assembly into AGOs.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adf0597</identifier><identifier>PMID: 36763664</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Argonaute Proteins - genetics ; Argonaute Proteins - metabolism ; Biochemistry ; Biomedicine and Life Sciences ; Cell Nucleus - metabolism ; Gene Expression Regulation ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Molecular Biology ; SciAdv r-articles</subject><ispartof>Science advances, 2023-02, Vol.9 (6), p.eadf0597</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. 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| subjects | Argonaute Proteins - genetics Argonaute Proteins - metabolism Biochemistry Biomedicine and Life Sciences Cell Nucleus - metabolism Gene Expression Regulation MicroRNAs - genetics MicroRNAs - metabolism Molecular Biology SciAdv r-articles |
| title | The Integrator complex regulates microRNA abundance through RISC loading |
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