Reference - Detail
RRC ID | 46389 |
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Author | Kudlow BA, Zhang L, Han M. |
Title | Systematic analysis of tissue-restricted miRISCs reveals a broad role for microRNAs in suppressing basal activity of the C. elegans pathogen response. |
Journal | Mol Cell |
Abstract |
Gene regulation by microRNAs (miRNAs) under specific physiological conditions often involves complex interactions between multiple miRNAs and a large number of their targets, as well as coordination with other regulatory mechanisms, limiting the effectiveness of classical genetic methods to identify miRNA functions. We took a systematic approach to analyze the miRNA-induced silencing complex (miRISC) in individual tissues of C. elegans and found that mRNAs encoded by pathogen-responsive genes were dramatically overrepresented in the intestinal miRISC, and that multiple miRNAs accumulated in the intestinal miRISCs upon infection. Inactivation of the miRISC or ablation of miRNAs from multiple families resulted in overexpression of several pathogen-responsive genes under basal conditions and, surprisingly, enhanced worm survival on pathogenic Pseudomonas aeruginosa. These results indicate that much of the miRNA activity in the gut is dedicated to attenuating the activity of the pathogen-response system, uncovering a complex physiological function of the miRNA network. |
Volume | 46(4) |
Pages | 530-41 |
Published | 2012-5-25 |
DOI | 10.1016/j.molcel.2012.03.011 |
PII | S1097-2765(12)00218-3 |
PMID | 22503424 |
PMC | PMC3365535 |
MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism Gene Expression Regulation Genes, Helminth Host-Pathogen Interactions / genetics Host-Pathogen Interactions / physiology Intestinal Mucosa / metabolism Intestines / microbiology MicroRNAs / genetics* MicroRNAs / metabolism* Muscles / metabolism Muscles / microbiology Pseudomonas aeruginosa / pathogenicity RNA, Helminth / genetics* RNA, Helminth / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism RNA-Induced Silencing Complex / genetics* RNA-Induced Silencing Complex / metabolism* Signal Transduction |
IF | 15.584 |
Times Cited | 31 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
Resource | |
C.elegans | tm3681 tm1863 tm2432 |