RRC ID 81500
Author Ghosh S, Chakraborti S, Devi D, Sahu R, Mandal S, Mandal L.
Title A conserved nutrient responsive axis mediates autophagic degradation of miRNA-mRNA hybrids in blood cell progenitors.
Journal Nucleic Acids Res
Abstract In animals, microRNAs are amongst the primary non-coding RNAs involved in regulating the gene expression of a cell. Most mRNAs in a cell are targeted by one or many miRNAs. Although several mechanisms can be attributed to the degradation of miRNA and mRNA within a cell, but the involvement of autophagy in the clearance of miRNA and its target mRNA is not known. We discover a leucine-responsive axis in blood cell progenitors that can mediate an autophagy-directed degradation of miRNA-bound mRNA in Drosophila melanogaster and Homo sapiens. This previously unknown miRNA clearance axis is activated upon amino acid deprivation that can traffic miRNA-mRNA-loaded Argonaute for autophagic degradation in a p62-dependent manner. Thus, our research not only reports a novel axis that can address the turnover of a catalytically active miRISC but also elucidates a slicer-independent mechanism through which autophagy can selectively initiate the clearance of target mRNA.
Volume 52(1)
Pages 385-403
Published 2024-1-11
DOI 10.1093/nar/gkad1047
PII 7442544
PMID 37994707
PMC PMC10783512
MeSH Animals Argonaute Proteins / genetics Argonaute Proteins / metabolism Autophagy / genetics Blood Cells Drosophila melanogaster / genetics Drosophila melanogaster / metabolism MicroRNAs* / genetics MicroRNAs* / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism
Resource
Drosophila DGRC#105442