Article
Multidisciplinary Sciences
Pengfei Ding, Siarhei Kharytonchyk, Nansen Kuo, Emily Cannistraci, Hana Flores, Ridhi Chaudhary, Mitali Sarkar, Xinmei Dong, Alice Telesnitsky, Michael F. Summers
Summary: The study reveals a bipartite mechanism for RNA packaging in HIV-1 assembly, involving both sequestration of the 5' cap and exposure of NC binding sites in the dimeric leader region. Certain elements and structures within the leader are crucial for efficient and accurate packaging.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Sayuri Sakuragi, Osamu Kotani, Masaru Yokoyama, Tatsuo Shioda, Hironori Sato, Jun-ichi Sakuragi
Summary: This study reveals that the dinucleotide pair at positions 226 and 227 within the psi segment of HIV-1 plays a critical role in regulating the packaging efficiency. Molecular genetic investigations and simulations suggest that nucleotide variations at these positions alter the structural dynamics of the psi element, affecting the binding interface of viral nucleocapsid protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Jennifer A. White, Fengting Wu, Saif Yasin, Milica Moskovljevic, Joseph Varriale, Filippo Dragoni, Angelica Camilo-Contreras, Jiayi Duan, Mei Y. Zheng, Ndeh F. Tadzong, Heer B. Patel, Jeanelle Mae C. Quiambao, Kyle Rhodehouse, Hao Zhang, Jun Lai, Subul A. Beg, Michael Delannoy, Christin Kilcrease, Christopher J. Hoffmann, Sebastien Poulin, Frederic Chano, Cecile Tremblay, Jerald Cherian, Patricia Barditch-Crovo, Natasha Chida, Richard D. Moore, Michael F. Summers, Robert F. Siliciano, Janet D. Siliciano, Francesco R. Simonetti
Summary: This study found that proviruses with 5'-leader defects in CD4+ T cell clones can cause persistent nonsuppressible viremia (NSV) in HIV-1 patients, which may complicate ART management.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Xin Yang, Yong Liu, Wen Cui, Mengmeng Liu, Wei Wang
Summary: During HIV-1 assembly, the conformation of the 5' leader (5'L) of viral genomic RNA (gRNA) dramatically affects Gag-RNA interactions and the selective packaging of gRNA dimers. The packaging conformation (5'L-P) of 5'L can bind more Gag molecules compared to the translation conformation (5'L-T), and the Gag-5'L-P complex is more stable at high salt concentrations. The NC-SP2-p6 region of Gag likely contributes to the faster association and slower dissociation kinetics for the Gag-5'L-P interaction and the higher stability.
Article
Biochemistry & Molecular Biology
Orian Gilmer, Elodie Mailler, Jean-Christophe Paillart, Assia Mouhand, Carine Tisne, Johnson Mak, Redmond P. Smyth, Roland Marquet, Valerie Vivet-Boudou
Summary: Maturation of HIV-1 viral particles is essential for infectivity. While the structural rearrangements of viral proteins during maturation are well-known, the maturation of genomic RNA (gRNA) structure is less explored. This study investigates the interactions between Pr55(Gag) or its maturation products and the gRNA region, revealing their distinct contributions to gRNA structural maturation.
Article
Multidisciplinary Sciences
Olga A. Nikolaitchik, Shuohui Liu, Jonathan P. Kitzrow, Yang Liu, Jonathan M. O. Rawson, Saurabh Shakya, Zetao Cheng, Vinay K. Pathak, Wei-Shau Hu, Karin Musier-Forsyth
Summary: HIV-1 differentiates between similar 1G and 3G RNAs based on their distinct structural ensembles, with 1G RNA exposing elements that promote dimerization and Gag binding for preferential packaging into viral particles.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Yaping Liu, Aldrex Munsayac, Ian Hall, Sarah C. Keane
Summary: The oncomiR-1, also known as the miR-17 similar to 92a polycistron, is overexpressed in multiple cancers and has oncogenic properties. The NPSL2 stem loop element is found to regulate the processing of pri-miR-92a, which is a constituent of oncomiR-1. The solution structure of NPSL2, which is the first high-resolution structure of an oncomiR-1 element, was determined using solution NMR spectroscopy. This study provides insights into the secondary and tertiary structure of an important RNA hairpin involved in miR biogenesis.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yusuke Sato, Akimasa Matsugami, Satoru Watanabe, Fumiaki Hayashi, Munehito Arai, Takanori Kigawa, Chiaki Nishimura
Summary: This study examined mutations and structures of HIV-1 capsid protein p24, highlighting the important roles of N-terminal beta structures and helices in the formation of p24 hexamers and pentamers. Additionally, wild-type p24 was found to adopt cis-conformation or trans-conformation during isomerization at G89-P90, with cis-conformation favoring interaction with cyclophilin-A.
Article
Biophysics
Robert J. Blakemore, Cleo Burnett, Canessa Swanson, Siarhei Kharytonchyk, Alice Telesnitsky, James B. Munro
Summary: Through fluorescence cross-correlation spectroscopy and single-molecule Forster resonance energy transfer imaging, we demonstrated that 5'UTRs from two different HIV-1 subtypes form kissing dimers (KDs) with divergent stabilities. Furthermore, both 5'UTRs convert to a stable dimer in the presence of the viral NC protein, adopting a conformation consistent with extensive intermolecular contacts. These results provide support for a unified model in which the genomes of diverse HIV-1 strains adopt an extended dimer (ED) conformation.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Camille Michiko Obayashi, Yoko Shinohara, Takao Masuda, Gota Kawai
Summary: The 5' -UTR of HIV-1 genomic RNA plays a crucial role in virus function, with different 5' -terminal sequences and structural characteristics affecting translation and reverse transcription reactions. The joint region between the TAR and PolyA stems has been shown to have small differences in the 5' -terminus, impacting the conformational characteristics of stem-loop structures. These findings highlight the importance of local conformation in the function of the 5' -UTR.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Olga A. Nikolaitchik, Saiful Islam, Jonathan P. Kitzrow, Alice Duchon, Zetao Cheng, Yang Liu, Jonathan M. O. Rawson, Wei Shao, Maria Nikolaitchik, Mary F. Kearney, Frank Maldarelli, Karin Musier-Forsyth, Vinay K. Pathak, Wei-Shau Hu, Malcolm Martin
Summary: HIV-1 uses host RNA polymerase II (Pol II) to transcribe its genome and employs multiple transcription start sites (TSS). Selection of TSS is regulated by specific sequences near the TATA box and R. Mutants expressing specific RNA transcripts with different numbers of guanosines at the 5'-end exhibit replication defects compared to the wild-type. These findings highlight the importance of TSS selection for HIV-1 replication fitness and genome integrity during reverse transcription.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Alice Duchon, Steven Santos, Jianbo Chen, Matthew Brown, Olga A. Nikolaitchik, Sheldon Tai, Jeffrey A. Chao, Eric O. Freed, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 Gag selects and packages the HIV RNA genome during virus assembly, with multimerization and plasma membrane anchoring properties playing critical roles in efficient genome packaging. Studying these properties can provide insights into the mechanisms of viral RNA packaging and assembly of infectious virions.
Article
Biochemistry & Molecular Biology
Camila Pereira-Montecinos, Daniela Toro-Ascuy, Catarina Ananias-Saez, Aracelly Gaete-Argel, Cecilia Rojas-Fuentes, Sebastian Riquelme-Barrios, Barbara Rojas-Araya, Francisco Garcia-de-Gracia, Paulina Aguilera-Cortes, Jonas Chnaiderman, Monica L. Acevedo, Fernando Valiente-Echeverria, Ricardo Soto-Rifo
Summary: This study reveals the regulatory role of N-6-methyladenosine (m(6)A) deposition on HIV-1 full-length RNA packaging, as well as the interaction between HIV-1 Gag protein and RNA demethylase FTO. The results show that m(6)A deposition leads to increased Gag synthesis and reduced packaging, while FTO-mediated demethylation promotes the incorporation of the full-length RNA into viral particles.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Omar Eladl, Yudai Yamaoki, Keiko Kondo, Takashi Nagata, Masato Katahira
Summary: It is important to understand the structure and interaction of RNA aptamers inside living cells to improve their potential as nucleic acid drugs. This study investigated the RNA aptamer TA for HIV-1 Tat and found that it forms two U-A*U base triples upon binding, which is critical for strong binding. In-cell NMR was used to reveal the complex structure and activity of TA in living human cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Makiha Fukuda, Jitong Cai, Joel S. Bader, Jef D. Boeke
Summary: A synthetic biology approach to constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. Understanding the structure-function relationships of RNA sequences is critical for the precise design of an artificial RNA replicon.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
