Presentation/Session Information

Session Information

Session Title: RNA Interference, Noncoding RNAs, and Genetic Technologies Session Type: Parallel
Session Location: Carnesale Palisades Ballroom Session Time: Sat, Jun 27 8:30AM - 11:30AM

Presentation Information

Program Number: 147 Presentation Time: 10:42AM - 10:54AM

Presentation Content

MORC-1 regulates endogenous small RNAs, chromatin organization, and germline immortality.Natasha Weiser 1,2, Danny Yang 1,3, Jayshree Khanikar 3, Suhua Feng 4, Raymond Chan 3, Steven Jacobsen 4, John Kim 1,3. 1)Life Sciences Institute, University of Michigan, Ann Arbor, MI; 2)Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI; 3)Department of Human Genetics, University of Michigan, Ann Arbor, MI; 4)Department of Molecular, Cellular, and Developmental Biology, University of California-Los Angeles, Los Angeles, CA

The germline is an immortal cell lineage. In C. elegans, epigenetic factors such as nuclear endogenous siRNAs (nuclear RNAi) and chromatin modifications are critical for maintaining germline immortality. Loss of these factors causes a mortal germline (Mrt) phenotype in which fertility declines over generations, eventually leading to complete sterility. As nuclear RNAi is inherited and leads to deposition of H3K9me3 at target genes, loss of the critical components of this pathway leads to loss of H3K9 trimethylation over generations. This transgenerational loss of heterochromatin is thought to contribute to the Mrt phenotype exhibited by nuclear RNAi mutants. However, the specific mechanism by which nuclear RNAi mediates heterochromatin deposition and germline mortality remains to be clarified.

We have identified MORC-1, a highly-conserved zinc-finger protein, as a novel factor which links the nuclear RNAi pathway to heterochromatin formation and germline mortality. MORC-1 is dispensable for biogenesis and inheritance of siRNAs but necessary for the effector function of the nuclear RNAi pathway. Accordingly, morc-1(-) mutants exhibit progressive defects in germline nuclear organization and a moderate defect in localization of H3K9 trimethylated foci at the nuclear periphery. MORC-1 contains an H3K4 reader domain and is excluded from H3K9me3 foci, suggesting that MORC-1 may be required for erasing euchromatin marks to allow for the formation of heterochromatin. In support of this hypothesis, the germline mortal phenotype of morc-1(-) worms can be rescued by mutations in the H3K4 methyltransferases, set-17 and set-30. Taken together, these data support a model in which MORC-1 may regulate the balance of active and silent chromatin by binding euchromatin to promote the removal of activating marks such as H3K4me3, thus allowing for the deposition of repressive H3K9me3 marks by the nuclear RNAi pathway. We are currently exploring the role of MORC-1 in establishment and maintenance of chromatin marks.




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