Structural basis for transcriptional start site control of HIV-1 RNA fate

被引：83

作者：

Brown, Joshua D. ^{[1
,2
]}

Kharytonchyk, Siarhei ^{[3
]}

Chaudry, Issac ^{[1
,2
]}

Iyer, Aishwarya S. ^{[1
,2
]}

Carter, Hannah ^{[1
,2
]}

Becker, Ghazal ^{[1
,2
]}

Desai, Yash ^{[1
,2
]}

Glang, Lindsay ^{[1
,2
]}

Choi, Seung H. ^{[1
,2
]}

Singh, Karndeep ^{[1
,2
]}

Lopresti, Michael W. ^{[1
,2
]}

Orellana, Matthew ^{[1
,2
]}

Rodriguez, Tatiana ^{[1
,2
]}

Oboh, Ubiomo ^{[1
,2
]}

Hijji, Jana ^{[1
,2
]}

Ghinger, Frances Grace ^{[1
,2
]}

Stewart, Kailan ^{[1
,2
]}

Francis, Dillion ^{[1
,2
]}

Edwards, Bryce ^{[1
,2
]}

Chen, Patrick ^{[1
,2
]}

Case, David A. ^{[4
,5
]}

Telesnitsky, Alice ^{[3
]}

Summers, Michael F. ^{[1
,2
]}

机构：

[1] Univ Maryland Baltimore Cty, Howard Hughes Med Inst, 1000 Hilltop Circle, Baltimore, MD 21250 USA

[2] Univ Maryland Baltimore Cty, Dept Chem & Biochem, 1000 Hilltop Circle, Baltimore, MD 21250 USA

[3] Univ Michigan, Med Sch, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[4] Rutgers State Univ, Dept Chem & Chem Biol, 610 Taylor Rd, Piscataway, NJ 08854 USA

[5] Rutgers State Univ, BioMaPS Inst, 610 Taylor Rd, Piscataway, NJ 08854 USA

来源：

SCIENCE | 2020年 / 368卷 / 6489期

基金：

美国国家卫生研究院;

关键词：

MULTIPLE SEQUENCE ALIGNMENT; VIRUS TYPE-1 RNA; STRUCTURE VALIDATION; NMR; DIMERIZATION; PARAMETERS; MOLPROBITY; INITIATION; MECHANISM; PROTEIN;

D O I：

10.1126/science.aaz7959

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines ((Cap)1G, (Cap)2G, or (Cap)3G, respectively) that are either selected for packaging as genomes ((Cap)1G) or retained in cells as translatable messenger RNAs (mRNAs) ((Cap)2G and (Cap)3G). To understand how 5'-guanosine number influences fate, we probed the structures of capped HIV-1 leader RNAs by deuterium-edited nuclear magnetic resonance. The (Cap)1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping. The (Cap)2G and (Cap)3G transcripts adopt an alternate structure with an elongated central helix, exposed splice donor residues, and an accessible cap. Extensive remodeling, achieved at the energetic cost of a G-C base pair, explains how a single 5'-guanosine modifies the function of a similar to 9-kilobase HIV-1 transcript.

引用

页码：413 / +

页数：32

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