title: Cargo sorting to lysosome-related organelles regulates siRNA-mediated gene silencing.
abstract: Mammals lacking BLOC-3 have impaired formation of melanosomes, a type of lysosome-related organelle (LRO), and, in earlier work, we found that a subunit of the BLOC-3 complex inhibits loading of Argonaute (Ago) proteins with small ribonucleic acids (RNAs) in Drosophila melanogaster cells. Small RNAs such as small interfering RNAs (siRNAs) direct Ago proteins to repress the stability of messenger RNA transcripts. In this paper, we show that BLOC-3 is required for biogenesis of Drosophila LROs called pigment granules. Other complexes that sort cargo to pigment LROs also negatively regulate siRNA activity. However, regulation is not obligately linked to biogenesis of LROs but instead to specific cargo-sorting processes. Negative regulation is also not linked to sorting into all LROs but only a specific class of pigment LRO. Thus, regulation of siRNA activity is tied to sorting of specific types of cargo to particular LROs.
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors: Dinari A
authors: DA
authors: Harris
authors: Kevin
authors: K
authors: Kim
authors: Kenji
authors: K
authors: Nakahara
authors: Constanza
authors: C
authors: Vásquez-Doorman
authors: Richard W
authors: RW
authors: Carthew
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D020868:Gene Silencing; D008247:Lysosomes / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D010860:Pigments, Biological / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics*
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D010860:Pigments, Biological; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex