SRタンパク質は7SKとプロモーター関連新生RNAと連携して,一時停止したポリメラーゼを放出します

Xiong Ji¹, Yu Zhou, Shatakshi Pandit

¹State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.

Cell

|May 14, 2013

まとめ

SRSF2は,新生RNAに結合することによって,プロモーター近接停止からポリメラーゼIIを放出する. この作用はP-TEFbを解放し,転写を活性化し,遺伝子発現を可能にします.

科学分野:

分子生物学は分子生物学である.
遺伝子規制遺伝子規制
RNA 生物学 RNA 生物学

背景:

哺乳類の遺伝子プロモーターの近くに停滞するRNAポリメラーゼII (RNAPII) は一般的です.
生産的伸縮への移行には,RNAP IIのキーキナーゼであるP-TEFbの徴募が必要です.
P-TEFbは7SK非コーディングRNAの阻害複合体で部分的に隔離されているが,転写活性化中に放出するメカニズムは不明であった.

研究の目的:

転写活性化中に7SK複合体からP-TEFbが放出されるメカニズムを調査する.
SRSF2 (SC35) のトランスクリプションパウズリリースと遺伝子活性化における役割を決定する.

主な方法:

遺伝子プロモーターにおける7SK複合体の組成を調べた.
P-TEFbの放出と転写の活性化におけるSRSF2の機能を評価した.
SRSF2とプロモーター関連新生RNAの相互作用を分析した.

主要な成果:

SRSF2は,遺伝子プロモーターの7SK複合体の構成要素である.
SRSF2は7SK複合体からSRSF2とP-TEFbのRNA依存の調整された放出を媒介する.
SRSF2がプロモーター関連新生RNAに結合すると,転写活性化が誘発されます.

結論:

SRSF2は,プロモーター近接停止からRNAP IIの放出に直接的な役割を果たしています.
プロモーター近接新生RNAは,細胞遺伝子の活性化に不可欠である.
HIV Tat/TARに類似するメカニズムは,細胞遺伝子の活性化に関与しています.

さらに関連する動画

10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

08:34

MS2-Affinity Purification Coupled with RNA Sequencing in Gram-Positive Bacteria

Published on: February 23, 2021

関連する概念動画

00:43

Bacterial RNA Polymerase

Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...

00:58

Eukaryotic RNA Polymerases

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...

01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...

02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can be...