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Comments on Kirshner, J.A. et al. (2019) International Worm Meeting "Investigating a role for MORC-1 in the CSR-1 gene licensing pathway." (0)
Overview
Kirshner, J.A., Weiser, N.E., Inoki, K., Mehta, N., & Kim, J.K. (2019). Investigating a role for MORC-1 in the CSR-1 gene licensing pathway presented in International Worm Meeting. Unpublished information; cite only with author permission.
In C. elegans, germline gene expression is regulated in part by endogenous small RNA (endo-siRNA) pathways. In particular, nuclear endo-siRNA pathways function to silence pseudogenes, transposons and protein-coding genes not intended for germline expression by inducing heterochromatin formation. An opposing small RNA-mediated pathway also exists to promotegermline gene expression. This pathway is governed by a distinct subset of endo-siRNAs that interact with the essential Argonaute, CSR-1, to promote transcription of target genes. This atypical "gene licensing" RNAi pathway is mechanistically poorly understood. We identified a role for the conserved Zinc-finger ATPase, MORC-1, in maintaining silencing downstream of nuclear RNAi. Unexpectedly, we uncovered a novel role for MORC-1 in the CSR-1 germline gene licensing pathway. MORC-1 physically interacts with CSR-1 and regulates CSR-1 target genes. Furthermore, morc-1 and csr-1 mutants genetically suppress each other. While morc-1(-) mutants display a germline mortal (Mrt) phenotype, in which the worms get progressively less fertile from one generation to the next,morc-1(-) mutants on csr-1 RNAi maintain fertility for many more generations than either single mutant alone. This rescue is accompanied by a restoration of gross germline morphology. We are currently using ChIP-seq to identify the chromatin targets of MORC-1 in purified germline nuclei. Taken together, we propose a mechanism by which the chromatin factor, MORC-1, regulates germline gene expression in both gene silencing and licensing pathways by preserving the proper local chromatin environment.
Affiliations:
- Harvard Medical School, Boston, MA
- Department of Biology, Johns Hopkins University, Baltimore, MD
- Life Sciences Institute, University of Michigan, Ann Arbor, MI