Regulation of Mammalian mRNA Decay
哺乳动物 mRNA 衰变的调控
基本信息
- 批准号:10387387
- 负责人:
- 金额:$ 5.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-01 至 2023-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenineCellsDNADiphosphatesDiseaseElementsEnzymesFlavinsFundingGene ExpressionGenetic TranscriptionGrantGuanosineHomeostasisHydrolaseIn VitroLinkMalignant NeoplasmsMessenger RNAMinorMolecularNicotinamide adenine dinucleotideNucleotidesOxidation-ReductionPost-Transcriptional RegulationProteinsProto-OncogenesRNARNA CapsRNA DecayRNA metabolismRegulationRoleStressTranslationsWorkclinical phenotypecofactorgenetic informationinsightmRNA DecaymRNA Stabilitynovel
项目摘要
Summary of the funded parental grant GM067005:
The control of mRNA stability is a critical determinant in the post-transcriptional regulation
of eukaryotic gene expression. Even minor alterations in mRNA stability can have
profound consequences and may manifest as clinical phenotypes as illustrated by the
ability of aberrantly expressed proto-oncogenes that can give rise to malignancies.
Eukaryotic mRNAs are generally thought to possess an N7 methyl guanosine (m7G) cap
at their 5¢ end to promote their stability and translation. However, our recent
demonstration that mammalian mRNAs can also carry a 5´-end nicotinamide adenine
dinucleotide (NAD) cap that in contrast to the m7G cap promotes mRNA decay, provides
a new paradigm for mRNA 5´ end processing and the contribution of nucleotide
metabolites in mRNA turnover. We now demonstrate that the redox state of NAD can also
modulate 3´ RNA decay with free NAD functioning as a cofactor to enhance RNA decay
and potentially providing a link to cellular energetics. Moreover, flavin adenine
diphosphate (FAD) can also serve as a 5´ cap on mammalian RNAs with Nudt16 and
DXO hydrolases functioning as proteins that can remove the FAD cap (deFADding) in
vitro. We will build on these novel findings throughout this proposal within three specific
aims. The first will address the functional role of free NAD on the control of 3´ end RNA
decay in vitro and delineate the molecular mechanism involved in its stimulation of decay.
The second will deduce changes in mRNA decay as a consequence of altered NAD levels
in cells and assess the regulatory role imparted by stress conditions in modulating RNA
decay through the control of NAD levels. In the last aim, we establish FAD cap as an
alternative RNA cap, identify FAD-capped RNAs and decipher the role of FAD caps and
the deFADding enzymes in cells. Collectively, the proposed studies will provide insight
into a heretofore unknown fundamental post-transcriptional regulatory mechanism and
will provide the framework for potential novel avenues to control gene expression in
normal and disease states.
获资助的父母补助金GM067005摘要:
项目成果
期刊论文数量(42)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The RNA binding protein HuR determines the differential translation of autism-associated FoxP subfamily members in the developing neocortex.
- DOI:10.1038/srep28998
- 发表时间:2016-07-07
- 期刊:
- 影响因子:4.6
- 作者:Popovitchenko T;Thompson K;Viljetic B;Jiao X;Kontonyiannis DL;Kiledjian M;Hart RP;Rasin MR
- 通讯作者:Rasin MR
BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.
- DOI:10.1186/scrt163
- 发表时间:2013-02-06
- 期刊:
- 影响因子:7.5
- 作者:Awe JP;Crespo AV;Li Y;Kiledjian M;Byrne JA
- 通讯作者:Byrne JA
5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.
- DOI:10.1016/j.cell.2017.02.019
- 发表时间:2017-03-09
- 期刊:
- 影响因子:64.5
- 作者:Jiao X;Doamekpor SK;Bird JG;Nickels BE;Tong L;Hart RP;Kiledjian M
- 通讯作者:Kiledjian M
DcpS as a therapeutic target for spinal muscular atrophy.
- DOI:10.1021/cb800120t
- 发表时间:2008-11-21
- 期刊:
- 影响因子:4
- 作者:Singh J;Salcius M;Liu SW;Staker BL;Mishra R;Thurmond J;Michaud G;Mattoon DR;Printen J;Christensen J;Bjornsson JM;Pollok BA;Kiledjian M;Stewart L;Jarecki J;Gurney ME
- 通讯作者:Gurney ME
Structure and function of pre-mRNA 5'-end capping quality control and 3'-end processing.
- DOI:10.1021/bi401715v
- 发表时间:2014-04-01
- 期刊:
- 影响因子:2.9
- 作者:Jurado AR;Tan D;Jiao X;Kiledjian M;Tong L
- 通讯作者:Tong L
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MEGERDITCH KILEDJIAN其他文献
MEGERDITCH KILEDJIAN的其他文献
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{{ truncateString('MEGERDITCH KILEDJIAN', 18)}}的其他基金
Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
- 批准号:
10443996 - 财政年份:2018
- 资助金额:
$ 5.56万 - 项目类别:
Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
- 批准号:
10797880 - 财政年份:2018
- 资助金额:
$ 5.56万 - 项目类别:
Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
- 批准号:
10622526 - 财政年份:2018
- 资助金额:
$ 5.56万 - 项目类别:
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