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The Integrator complex regulates microRNA abundance through RISC loading.

Nina KirsteinSadat DokaneheifardPradeep Reddy CingaramMonica Guiselle ValenciaFelipe Cesar BeckedorffHelena Gomes Dos SantosEzra BlumenthalMina Masoumeh TayariGabriel Stephen GaidoshRamin Shiekhattar
Published in: Science advances (2023)
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.
Keyphrases
  • antibiotic resistance genes
  • protein protein
  • binding protein
  • oxidative stress
  • wastewater treatment
  • microbial community