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
- 来源:
- 关键词:7SL RNAAllelesAlu ElementsBindingBiochemicalBiologicalBiological AssayBiologyCRISPR/Cas technologyCandidate Disease GeneCanis familiarisCategoriesCell LineCellsCellular AssayChemicalsCis-Acting SequenceCollaborationsComplementCultured CellsDNA Transposable ElementsDNA sequencingDataElementsEventEvolutionExonsGenerationsGeneticGenomeGenomic DNAGenomicsGoalsHela CellsHumanIntegration Host FactorsIntronsKnock-outLaboratoriesLeadLocationLong Interspersed ElementsMalignant NeoplasmsMapsMediatingMichiganMobile Genetic ElementsModelingMolecularMusMutationOpen Reading FramesPaste substancePoly(A) TailProcessProteinsRNARNA SequencesRetrotranspositionRetrotransposonRibonucleoproteinsRibosomesShort Interspersed Nucleotide ElementsSignal Recognition ParticleStructural ModelsStructureTechnologyTestingTransfer RNAUniversitiesUntranslated RNAbasecausal variantdifferential expressiondisease phenotypeexperimental studyhuman diseasemammalian genomeparticletranscriptome sequencingwhole genome
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:
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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