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Elucidation of Integrator's Function

积分器功能说明

基本信息

批准号：
8308483
负责人：
RAMIN SHIEKHATTAR
金额：
$ 38.65万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8308483
关键词：
Biochemical Boxing C-terminal Cell Cycle Regulation Cell Line Cell Proliferation Cis-Acting Sequence Cleavage And Polyadenylation Specificity Factor Code Complex Cytoplasm DDX26 gene Data Functional RNA Gene Expression Regulation Genes Genetic Transcription Growth In Vitro Individual Lead Malignant Epithelial Cell Mediating Messenger RNA Molecular Names Non-Small-Cell Lung Carcinoma Nuclear Nucleotides Pattern Phosphorylation Play Process Prostate carcinoma Proteins RNA 3&apos End Processing RNA Polymerase II RNA Precursors RNA Processing RNA polymerase II largest subunit Recombinants Recruitment Activity Regulation Role Seminal Small Nuclear RNA Spliceosomes Testing Transcript Transcription Process Transcriptional Regulation Tumor Suppressor Genes Tumor Suppressor Proteins U1 small nuclear RNA U2 small nuclear RNA Work design in vivo insight mRNA Precursor metaplastic cell transformation novel polypeptide promoter protein complex public health relevance reconstitution research study tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Project Summary: The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein coding genes. A large body of data also implicates the CTD in the transcription and processing of RNAPII-mediated small nuclear RNA (snRNA) genes. However, the identity of the complex(es) that associate with the CTD and mediate the processing of snRNA genes have remained elusive. We describe an RNA polymerase II complex that contains at least twelve novel subunits, termed the Integrator, in addition to core RNAPII subunits. Two of the Integrator subunits display similarities to the subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates their 3'-end processing. The Integrator complex is evolutionarily conserved in metazoans and directly interacts with the C- terminal domain of the RNA polymerase II large subunit. This proposal is focused at elucidating the role of the Integrator, in control of transcription and cellular proliferation. The three Aims are designed to provide a thorough physical and functional characterization of the Integrator complex. Aim1 describes experiments that will begin to define the function of the individual proteins in the complex and details the functional reconstitution of Integrator. Aim2 describes a detailed functional analysis of Integrator in transcriptional regulation of snRNA genes and extend the work to analysis of other non-coding RNA and RNAPII-mediated genes. Aim3 extends the work by analyzing the role of the complex and its individual subunits in oncogenesis and cell cycle regulation. Elucidation of the mechanism through which small nuclear RNAs are transcribed and processed to mature RNAs is of seminal importance in understanding regulation of gene expression and growth control. Aberrant regulation of small nuclear RNA processing could result in defective messenger RNA processing through deregulation of splicesome and may lead to cellular transformation and oncogenesis. PUBLIC HEALTH RELEVANCE: Public Health Relevance Elucidation of the mechanism through which small nuclear RNAs are transcribed and processed to mature RNAs is of seminal importance in understanding regulation of gene expression and growth control. Aberrant regulation of small nuclear RNA processing could result in defective messenger RNA processing through deregulation of splicesome and may lead to cellular transformation and oncogenesis.

描述（由申请人提供）：