RNA聚合酶Ⅱ启动子近端暂停/释放的动态调控及生理作用研究进展

doi:10.19586/j.2095-2341.2022.0037

生物技术进展 ›› 2022, Vol. 12 ›› Issue (5): 705-710.DOI: 10.19586/j.2095-2341.2022.0037

RNA聚合酶Ⅱ启动子近端暂停/释放的动态调控及生理作用研究进展

乔朝辉(), 陈亮()

武汉大学生命科学学院，武汉 430072

收稿日期:2022-03-17 接受日期:2022-05-05 出版日期:2022-09-25 发布日期:2022-09-30
通讯作者: 陈亮
作者简介:乔朝辉 E-mail：18710663466@163.com；
基金资助:
国家自然科学基金项目(32171289)

Dynamic Regulation and Physiological Role of Promoter-proximal Pause/Release of RNA Polymerase Ⅱ: a Review

Zhaohui QIAO(), Liang CHEN()

College of Life Sciences，Wuhan University，Wuhan 430072，China

Received:2022-03-17 Accepted:2022-05-05 Online:2022-09-25 Published:2022-09-30
Contact: Liang CHEN

摘要/Abstract

摘要：

基因表达的精确时空调控对生物体的发育和生存至关重要。在多数后生动物中，RNA聚合酶Ⅱ（RNA polymerase Ⅱ，RNAPⅡ）在发育和应激反应相关基因的启动子近端区域暂停，一旦受到环境或发育信号的刺激，RNAPⅡ从启动子近端向基因体（gene body）释放，进行有效延伸。RNAPⅡ在基因转录起始位点下游近端区域的暂停/释放是基因转录过程的必要环节，也是基因表达调控的关键步骤，与基因表达时空调控及多种人类疾病密切相关。综述了参与RNAPⅡ启动子近端暂停的维持和释放的调控机制的研究进展，重点探讨了其在机体发育的重要调控作用及其与其他基因调控机制的联系，并展望了RNAPⅡ启动子近端暂停与释放研究中的潜在问题和未来研究方向，以期为进一步解析RNAPⅡ启动子近端暂停与释放的调控机制及其在发育中的作用提供线索。

关键词: RNA聚合酶Ⅱ, 启动子近端暂停, 转录延伸, 发育

Abstract:

Precise temporal and spatial regulation of gene expression is important for the development and survival of organisms. In most metazoans， RNA polymerase Ⅱ （RNAPⅡ） pauses in the promoter-proximal region of genes related to development and stress response. Once stimulated by environmental or developmental signals， RNAPⅡ is released from the promoter to the gene body for effective extension. The promoter-proximal pausing/pause release of RNAPⅡ at the downstream of transcriptional start site provides an important layer of regulation on RNAPⅡ activity in the promoter region and is closely related to spatial-temporal regulation of gene expression and a variety of human diseases. This paper aimed to review recent progress in studying the regulation mechanism of RNAPⅡ promoter-proximal pause， explored important roles of promoter-proximal pause/release of RNAPⅡ in development and its potential relationship with other gene regulation mechanisms. This report also summarized the potential questions and research directions in this filed， in order to provide clues to clarify the molecular mechanism and roles of RNAPⅡ promoter-proximal pause/release in development.

Key words: RNA polymerase Ⅱ, promoter-proximal pause, transcription elongation, development

中图分类号:

Q943

乔朝辉, 陈亮. RNA聚合酶Ⅱ启动子近端暂停/释放的动态调控及生理作用研究进展[J]. 生物技术进展, 2022, 12(5): 705-710.

Zhaohui QIAO, Liang CHEN. Dynamic Regulation and Physiological Role of Promoter-proximal Pause/Release of RNA Polymerase Ⅱ: a Review[J]. Current Biotechnology, 2022, 12(5): 705-710.

参考文献 49

1	SCHIER A C, TAATJES D J. Structure and mechanism of the RNA polymerase Ⅱ transcription machinery[J]. Genes Dev., 2020, 34(7-8): 465-488.
2	CORE L, ADELMAN K. Promoter-proximal pausing of RNA polymerase Ⅱ‍: A nexus of gene regulation[J]. Genes Dev., 2019, 33(15-16): 960-982.
3	PROUDFOOT N J. Transcriptional termination in mammals: Stopping the RNA polymerase Ⅱ juggernaut[J/OL]. Science, 2016, 352(6291): aad9926[2022-06-25]. .
4	ADELMAN K, LIS J T. Promoter-proximal pausing of RNA polymerase Ⅱ: emerging roles in metazoans[J]. Nat. Rev. Genet., 2012, 13(10): 720-731.
5	YAMAGUCHI Y, SHIBATA H, HANDA H. Transcription elongation factors DSIF and NELF: promoter-proximal pausing and beyond[J]. Biochim. Biophys. Acta, 2013, 1829(1): 98-104.
6	VOS S M, FARNUNG L, URLAUB H, et al.. Structure of paused transcription complex Pol Ⅱ-DSIF-NELF[J]. Nature, 2018, 560(7720): 601-606.
7	AOI Y, SMITH E R, SHAH A P, et al.. NELF Regulates a promoter-proximal step distinct from RNA Pol Ⅱ pause-release[J]. Mol. Cell, 2020, 78(2): 261-274.
8	CHENG B, LI T, RAHL P B, et al.. Functional association of Gdown1 with RNA polymerase Ⅱ poised on human genes[J]. Mol Cell, 2012, 45(1): 38-50.
9	LEE C, LI X, HECHMER A, et al.. NELF and GAGA factor are linked to promoter-proximal pausing at many genes in Drosophila[J]. Mol. Cell Biol., 2008, 28(10): 3290-300.
10	CHEN F X, WOODFIN A R, GARDINI A, et al.. PAF1, a molecular regulator of promoter-proximal pausing by RNA polymerase Ⅱ‍[J]. Cell, 2015, 162(5): 1003-1015.
11	YU M, YANG W, NI T, et al.. RNA polymerase Ⅱ-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase Ⅱ[J]. Science, 2015, 350(6266): 1383-1386.
12	FANT C B, LEVANDOWSKI C B, GUPTA K, et al.. TFⅡD Enables RNA polymerase Ⅱ promoter-proximal pausing[J]. Mol. Cell, 2020, 78(4): 785-793.
13	CHEN F X, SMITH E R, SHILATIFARD A. Born to run: control of transcription elongation by RNA polymerase Ⅱ[J]. Nat. Rev. Mol. Cell Biol., 2018, 19(7): 464-478.
14	LI Y, LIU M, CHEN L F, et al.. P-TEFb: finding its ways to release promoter-proximally paused RNA polymerase Ⅱ[J]. Transcription, 2018, 9(2): 88-94.
15	JI X, ZHOU Y, PANDIT S, et al.. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase[J]. Cell, 2013, 153(4): 855-868.
16	CALO E, FLYNN R A, MARTIN L, et al.. RNA helicase DDX21 coordinates transcription and ribosomal RNA processing[J]. Nature, 2015, 518(7538): 249-253.
17	KANNO T, KANNO Y, LEROY G, et al.. BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones[J]. Nat. Struct. Mol. Biol., 2014, 21(12): 1047-1057.
18	KOMARNITSKY P, CHO E J, BURATOWSKI S. Different phosphorylated forms of RNA polymerase Ⅱ and associated mRNA processing factors during transcription[J]. Genes Dev., 2000, 14(19): 2452-2460.
19	ADELMAN K, MARR M T, WERNER J, et al.. Efficient release from promoter-proximal stall sites requires transcript cleavage factor TFⅡS[J]. Mol. Cell, 2005, 17(1): 103-112.
20	YADAV D, GHOSH K, BASU S, et al.. Multivalent role of human TFⅡD in recruiting elongation components at the promoter-proximal region for transcriptional control[J]. Cell Rep., 2019, 26(5): 1303-1317.
21	RAHL P B, LIN C Y, SEILA A C, et al.. c-Myc regulates transcriptional pause release[J]. Cell, 2010, 141(3): 432-445.
22	STEINPARZER I, SEDLYAROV V, RUBIN J D, et al.. transcriptional responses to IFN-gamma require mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions[J]. Mol. Cell, 2019, 76(3): 485-499.
23	DONNER A J, EBMEIER C C, TAATJES D J, et al.. CDK8 is a positive regulator of transcriptional elongation within the serum response network[J]. Nat. Struct. Mol. Biol., 2010, 17(2): 194-201.
24	MCNAMARA R P, REEDER J E, MCMILLAN E A, et al.. KAP1 recruitment of the 7SK snRNP complex to promoters enables transcription elongation by RNA polymerase Ⅱ‍[J]. Mol. Cell, 2016, 61(1): 39-53.
25	BARBORIC M, NISSEN R M, KANAZAWA S, et al.. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase Ⅱ[J]. Mol. Cell, 2001, 8(2): 327-337.
26	EBERHARDY S R, FARNHAM P J. c-Myc mediates activation of the cad promoter via a post-RNA polymerase Ⅱ recruitment mechanism[J]. J. Biol. Chem., 2001, 276(51): 48562-48571.
27	LUECKE H F, YAMAMOTO K R. The glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression[J]. Genes Dev., 2005, 19(9): 1116-1127.
28	OVEN I, BRDICKOVA N, KOHOUTEK J, et al.. AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells[J]. Mol. Cell Biol., 2007, 27(24): 8815-8823.
29	GILMOUR D S, LIS J T. RNA polymerase Ⅱ interacts with the promoter region of the noninduced hsp70 gene in Drosophila melanogaster cells[J]. Mol Cell Biol, 1986, 6(11): 3984-3989.
30	ZEITLINGER J, STARK A, KELLIS M, et al.. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo[J]. Nat. Genet., 2007, 39(12): 1512-1516.
31	SHAO W, ALCANTARA S G, ZEITLINGER J. Reporter-ChIP-nexus reveals strong contribution of the Drosophila initiator sequence to RNA polymerase pausing[J/OL]. Elife, 2019, 8:e41461[2022-06-25]. .
32	CHEN K, JOHNSTON J, SHAO W, et al.. A global change in RNA polymerase Ⅱ pausing during the Drosophila midblastula transition [J/OL]. Elife, 2013, 2: e00861[2022-06-25]. .
33	BOETTIGER A N, LEVINE M. Synchronous and stochastic patterns of gene activation in the Drosophila embryo[J]. Science, 2009, 325(5939): 471-473.
34	JENNINGS B H, SHAH S, YAMAGUCHI Y, et al.. Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila [J]. Curr. Biol., 2004, 14(18): 1680-1684.
35	WANG X, HANG S, PRAZAK L, et al.. NELF potentiates gene transcription in the Drosophila embryo[J/OL]. PLoS ONE, 2010, 5(7): e11498[2022-06-15]. .
36	AMLEH A, NAIR S J, SUN J, et al.. Mouse cofactor of BRCA1 (Cobra1) is required for early embryogenesis[J/OL]. PLoS ONE, 2009, 4(4): e5034[2022-06-25]. .
37	LAGHA M, BOTHMA J P, ESPOSITO E, et al.. Paused Pol Ⅱ coordinates tissue morphogenesis in the Drosophila embryo[J]. Cell, 2013, 153(5): 976-987.
38	LIU X, GOGATE A A, TASTEMEL M, et al.. Dynamic change of transcription pausing through modulating NELF protein stability regulates granulocytic differentiation[J]. Blood Adv., 2017, 1(18): 1358-1367.
39	GUO S, YAMAGUCHI Y, SCHILBACH S, et al.. A regulator of transcriptional elongation controls vertebrate neuronal development[J]. Nature, 2000, 408(6810): 366-369.
40	GATES L A, SHI J, ROHIRA A D, et al.. Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation[J]. J. Biol. Chem., 2017, 292(35): 14456-14472.
41	ETCHEGARAY J P, ZHONG L, LI C, et al.. The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing[J]. Mol. Cell, 2019, 75(4): 683-699.
42	VAID R, WEN J, MANNERVIK M. Release of promoter-proximal paused Pol Ⅱ in response to histone deacetylase inhibition[J]. Nucl. Acids Res., 2020, 48(9): 4877-4890.
43	HUANG K L, JEE D, STEIN C B, et al.. Integrator recruits protein phosphatase 2A to prevent pause release and facilitate transcription termination[J]. Mol. Cell, 2020, 80(2): 345-358.
44	SHRESTHA P, XIAO S, DHAKAL S, et al.. Nascent RNA transcripts facilitate the formation of G-quadruplexes[J]. Nucl. Acids Res., 2014, 42(11): 7236-7346.
45	CHEN L, CHEN J Y, ZHANG X, et al.. R-ChIP using inactive RNase H reveals dynamic coupling of r-loops with transcriptional pausing at gene promoters[J]. Mol. Cell, 2017, 68(4): 745-757.
46	ZHANG X, CHIANG H C, WANG Y, et al.. Attenuation of RNA polymerase Ⅱ pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis[J/OL]. Nat. Commun., 2017, 8: 15908 [2022-06-15]. .
47	CHEN L, CHEN J Y, HUANG Y J, et al.. The augmented R-Loop Is a unifying mechanism for myelodysplastic syndromes induced by high-risk splicing factor mutations[J]. Mol. Cell, 2018, 69(3): 412-425.
48	JAUREGUI-LOZANO J, ESCOBEDO S, EASTON A, et al.. Proper control of R-loop homeostasis is required for maintenance of gene expression and neuronal function during aging[J/OL]. Aging Cell, 2022, 21(2): e13554 [2022-06-15]. .
49	ALECKI C, CHIWARA V, SANZ L A, et al.. RNA-DNA strand exchange by the Drosophila polycomb complex PRC2[J/OL]. Nat. Commun., 2020, 11(1): 1781 [2022-06-15]. .

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RNA聚合酶Ⅱ启动子近端暂停/释放的动态调控及生理作用研究进展

Dynamic Regulation and Physiological Role of Promoter-proximal Pause/Release of RNA Polymerase Ⅱ: a Review

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