TY - JOUR
T1 - Cargo sorting to lysosome-related organelles regulates siRNA-mediated gene silencing
AU - Harris, Dinari A.
AU - Kim, Kevin
AU - Nakahara, Kenji
AU - Vásquez-Doorman, Constanza
AU - Carthew, Richard W.
PY - 2011/7/11
Y1 - 2011/7/11
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201102021
DO - 10.1083/jcb.201102021
M3 - Article
C2 - 21746852
AN - SCOPUS:79960232278
SN - 0021-9525
VL - 194
SP - 77
EP - 87
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -