Identification of Factors Critical for SINE Retrotransposition

确定 SINE 逆转位的关键因素

基本信息

  • 批准号:
    10095880
  • 负责人:
  • 金额:
    $ 47.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-12-02 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

Abstract Short INterspersed Elements (SINEs) are mobile genetic elements that are present in all mammalian genomes. Most mammalian SINEs can be subdivided into two general categories: (1) those derived from 7SL signal recognition particle RNA (e.g., human Alu elements); and (2) those derived from transfer RNAs (e.g., canine SINEC_Cf elements). Alu and SINEC_Cf elements have had a major impact on genome evolution and comprise an astounding ~11% and ~15% of human and canine genomic DNA, respectively. The vast majority of SINEs have been rendered immobile by mutational processes; however, some human-specific Alu elements and canine SINEC_Cf elements can mobilize to new genomic locations by a “copy and paste” mechanism termed retrotransposition. To date, greater than 76 independent germline Alu retrotransposition events have been implicated as the cause of human diseases, including cancer. SINEC_Cf retrotransposition events are responsible for various diseases and phenotypic differences in canines. SINEs do not encode proteins; thus, they are classified as `non-autonomous' retrotransposons. Previous studies, including our preliminary data, demonstrate that a protein encoded by an autonomous Long INterspersed Element-1 (LINE-1) retrotransposon (LINE-1 ORF2p) is required for Alu and SINEC_Cf element retrotransposition. We hypothesize that the structure of Alu RNA, and by extension SINEC_Cf RNA, and unidentified host factor(s) allow these RNAs to localize to the ribosome, where they can compete with the LINE-1 poly(A) tail for LINE-1 ORF2p binding to promote their retrotransposition. Here, we propose to use a combination of molecular biological, evolutionary inference, genetic, genomic, and biochemical approaches to: (1) use established RNA secondary structure models, Illumina-based SHAPE-MaP chemical probing, and established cultured cell assays to uncover cis- acting RNA structures and sequences required for human-specific Alu and SINEC_Cf retrotransposition; and (2) exploit differences between HeLa cell isolates that differ in their ability to support Alu and SINEC_Cf retrotransposition to identify host factor(s) critical for SINE retrotransposition. This proposal builds on successful collaborations between the Moran and Kidd laboratories at the University of Michigan and will combine the Moran laboratory's expertise in transposable element and RNA biology with the Kidd laboratory's expertise in computational and statistical genomics and evolutionary biology to elucidate SINE retrotransposition mechanisms.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Jeffrey M Kidd其他文献

Genome sequencing and analysis of admixed genomes of African and Mexican ancestry: implications for personal ancestry reconstruction and multi-ethnic medical genomics
非洲和墨西哥血统混合基因组的基因组测序与分析:对个人血统重建和多族裔医学基因组学的意义
  • DOI:
    10.1186/gb-2010-11-s1-o4
  • 发表时间:
    2010-10-11
  • 期刊:
  • 影响因子:
    9.400
  • 作者:
    Francisco M De La Vega;Katarzyna Bryc;Jeremiah D Degehnardt;Shaila Musharoff;Jeffrey M Kidd;Vrunda Seth;Sarah Stanley;Abra Brisbin;Alon Keinan;Andrew Clark;Carlos D Bustamante
  • 通讯作者:
    Carlos D Bustamante

Jeffrey M Kidd的其他文献

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{{ truncateString('Jeffrey M Kidd', 18)}}的其他基金

Identification of Factors Critical for SINE Retrotransposition
确定 SINE 逆转位的关键因素
  • 批准号:
    10311056
  • 财政年份:
    2020
  • 资助金额:
    $ 47.58万
  • 项目类别:
HIV-1 Genomic RNA Integrity
HIV-1 基因组 RNA 完整性
  • 批准号:
    10010448
  • 财政年份:
    2020
  • 资助金额:
    $ 47.58万
  • 项目类别:
HIV-1 Genomic RNA Integrity
HIV-1 基因组 RNA 完整性
  • 批准号:
    10241263
  • 财政年份:
    2020
  • 资助金额:
    $ 47.58万
  • 项目类别:
Identification of Factors Critical for SINE Retrotransposition
确定 SINE 逆转位的关键因素
  • 批准号:
    10527360
  • 财政年份:
    2020
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8537229
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8413227
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8915986
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8213131
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8715423
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:
Characterizing the Global Architecture of Genomic Diversity
描述基因组多样性的全球结构
  • 批准号:
    8335440
  • 财政年份:
    2011
  • 资助金额:
    $ 47.58万
  • 项目类别:

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