Person:
Shi, Zhen

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Shi

First Name

Zhen

Name

Shi, Zhen

Filters

2012 - 20132

Settings

Author's Publications: search.filters.isAuthorOfPublication.05b3c406-fec1-4bb4-a7fc-ae1d65b5996e

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Genetic and genomic analysis of small RNA pathways in nematodes
    (2013-10-15) Shi, Zhen; Ruvkun, Gary B.; Moazed, Danesh; Blower, Michael; Vasudevan, Shobha; Walhout, Marian
    Small noncoding RNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and endogenous small-interfering RNAs (endo-siRNAs), regulate developmental and defense pathways in animals. While many small RNA silencing protein cofactors have been identified, much more is to be learned from a dynamic and quantitative perspective to reveal the underlying mechanisms and designing principles of each pathway. In this dissertation, I present studies that examine the temporal dynamics of small RNA pathways - one from an evolutionary time scale among the nematode species, and one from finely staged Caenorabditis elegans during the first larval stage. I also describe works identifying new cofactors functions in the miRNA pathway, potentially through regulating the spatial dynamics of the miRNA silencing complex.
  • Thumbnail Image
    Publication
    Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma Pathway Chromatin Complexes
    (Public Library of Science, 2012) Wu, Xiaoyun; Shi, Zhen; Cui, Mingxue; Han, Min; Ruvkun, Gary
    The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.