Comparison of SIV and HIV-1 Genomic RNA Structures Reveals Impact of Sequence Evolution on Conserved and Non-Conserved Structural Motifs

PLoS Pathogens

Robert J. Gorelick¹  Ronald Swanstrom²  Elizabeth Pollom²  Christina L. Burch³  Kristen K. Dang⁴  E. Lake Potter⁵  Kevin M. Weeks⁵ 

[1] AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America;Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

关键词: RNA structure;    Mammalian genomics;    Viral structure;    Sequence motif analysis;    Sequence alignment;    HIV-1;    Guanosine;    Comparative genomics;   

DOI  :  10.1371/journal.ppat.1003294

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

RNA secondary structure plays a central role in the replication and metabolism of all RNA viruses, including retroviruses like HIV-1. However, structures with known function represent only a fraction of the secondary structure reported for HIV-1NL4-3. One tool to assess the importance of RNA structures is to examine their conservation over evolutionary time. To this end, we used SHAPE to model the secondary structure of a second primate lentiviral genome, SIVmac239, which shares only 50% sequence identity at the nucleotide level with HIV-1NL4-3. Only about half of the paired nucleotides are paired in both genomic RNAs and, across the genome, just 71 base pairs form with the same pairing partner in both genomes. On average the RNA secondary structure is thus evolving at a much faster rate than the sequence. Structure at the Gag-Pro-Pol frameshift site is maintained but in a significantly altered form, while the impact of selection for maintaining a protein binding interaction can be seen in the conservation of pairing partners in the small RRE stems where Rev binds. Structures that are conserved between SIVmac239 and HIV-1NL4-3 also occur at the 5′ polyadenylation sequence, in the plus strand primer sites, PPT and cPPT, and in the stem-loop structure that includes the first splice acceptor site. The two genomes are adenosine-rich and cytidine-poor. The structured regions are enriched in guanosines, while unpaired regions are enriched in adenosines, and functionaly important structures have stronger base pairing than nonconserved structures. We conclude that much of the secondary structure is the result of fortuitous pairing in a metastable state that reforms during sequence evolution. However, secondary structure elements with important function are stabilized by higher guanosine content that allows regions of structure to persist as sequence evolution proceeds, and, within the confines of selective pressure, allows structures to evolve.

【 授权许可】

CC BY