Comparative Mutational Analysis of Cis-acting RNA Signals for Translational Frameshifting in HIV-1 and HTLV-2

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2001 Feb 27

PMID 11222762

Citations 37

Authors

Y G Kim

S Maas

A Rich

Affiliations

Soon will be listed here.

Abstract

Human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type II (HTLV-2) use a similar mechanism for -1 translational frameshifting to overcome the termination codon in viral RNA at the end of the gag gene. Previous studies have identified two important RNA signals for frameshifting, the slippery sequence and a downstream stem-loop structure. However, there have been somewhat conflicting reports concerning the individual contributions of these sequences. In this study we have performed a comprehensive mutational analysis of the cis-acting RNA sequences involved in HIV-1 gag-pol and HTLV-2 gag-pro frameshifting. Using an in vitro translation system we determined frameshifting efficiencies for shuffled HIV-1/HTLV-2 RNA elements in a background of HIV-1 or HTLV-2 sequences. We show that the ability of the slippery sequence and stem-loop to promote ribosomal frameshifting is influenced by the flanking upstream sequence and the nucleotides in the spacer element. A wide range of frameshift efficiency rates was observed for both viruses when shuffling single sequence elements. The results for HIV-1/HTLV-2 chimeric constructs represent strong evidence supporting the notion that the viral wild-type sequences are not designed for maximal frameshifting activity but are optimized to a level suited to efficient viral replication.

Citing Articles

Abracadabra, One Becomes Two: The Importance of Context in Viral -1 Programmed Ribosomal Frameshifting.

Penn W, Mukhopadhyay S mBio. 2022; 13(4):e0246821.

PMID: 35735745 PMC: 9426525. DOI: 10.1128/mbio.02468-21.

Premature translation termination mediated non-ER stress induced ATF6 activation by a ligand-dependent ribosomal frameshifting circuit.

Hsu H, Murata A, Dohno C, Nakatani K, Chang K Nucleic Acids Res. 2022; 50(9):5369-5383.

PMID: 35511080 PMC: 9122530. DOI: 10.1093/nar/gkac257.

From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion.

Atkins J, OConnor K, Bhatt P, Loughran G Viruses. 2021; 13(7).

PMID: 34199077 PMC: 8310308. DOI: 10.3390/v13071251.

V, 2.Ribosomal frameshifting in astroviruses.

Brierley I, Vidakovic M Perspect Med Virol. 2020; 9:587-606.

PMID: 32287603 PMC: 7133818. DOI: 10.1016/S0168-7069(03)09035-9.

An RNA pseudoknot stimulates HTLV-1 programmed -1 ribosomal frameshifting.

Thulson E, Hartwick E, Cooper-Sansone A, Williams M, Soliman M, Robinson L RNA. 2020; 26(4):512-528.

PMID: 31980578 PMC: 7075266. DOI: 10.1261/rna.070490.119.

References

Kim Y, Su L, Maas S, ONeill A, Rich A . Specific mutations in a viral RNA pseudoknot drastically change ribosomal frameshifting efficiency. Proc Natl Acad Sci U S A. 1999; 96(25):14234-9. PMC: 24420. DOI: 10.1073/pnas.96.25.14234. View

Karacostas V, Wolffe E, Nagashima K, Gonda M, Moss B . Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles. Virology. 1993; 193(2):661-71. DOI: 10.1006/viro.1993.1174. View

Farabaugh P . Translational frameshifting: implications for the mechanism of translational frame maintenance. Prog Nucleic Acid Res Mol Biol. 2000; 64:131-70. DOI: 10.1016/s0079-6603(00)64004-7. View

Lucchesi J, Makelainen K, Merits A, Tamm T, Makinen K . Regulation of -1 ribosomal frameshifting directed by cocksfoot mottle sobemovirus genome. Eur J Biochem. 2000; 267(12):3523-9. DOI: 10.1046/j.1432-1327.2000.01379.x. View

Ban N, Nissen P, Hansen J, Moore P, Steitz T . The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000; 289(5481):905-20. DOI: 10.1126/science.289.5481.905. View

Kim Y, Maas S, Wang S, Rich A . Mutational study reveals that tertiary interactions are conserved in ribosomal frameshifting pseudoknots of two luteoviruses. RNA. 2000; 6(8):1157-65. PMC: 1369989. DOI: 10.1017/s1355838200000510. View

Schluenzen F, Tocilj A, Zarivach R, Harms J, Gluehmann M, Janell D . Structure of functionally activated small ribosomal subunit at 3.3 angstroms resolution. Cell. 2000; 102(5):615-23. DOI: 10.1016/s0092-8674(00)00084-2. View

Wimberly B, Brodersen D, Clemons Jr W, Morgan-Warren R, Carter A, Vonrhein C . Structure of the 30S ribosomal subunit. Nature. 2000; 407(6802):327-39. DOI: 10.1038/35030006. View

Steitz J . Polypeptide chain initiation: nucleotide sequences of the three ribosomal binding sites in bacteriophage R17 RNA. Nature. 1969; 224(5223):957-64. DOI: 10.1038/224957a0. View

10.

Kuechler E, Rich A . Position of the initiator and peptidyl sites in the E. coli ribosome. Nature. 1970; 225(5236):920-4. DOI: 10.1038/225920a0. View

11.

Kang C, Cantor C . Structure of ribosome-bound messenger RNA as revealed by enzymatic accessibility studies. J Mol Biol. 1985; 181(2):241-51. DOI: 10.1016/0022-2836(85)90088-9. View

12.

Jacks T, Power M, Masiarz F, Luciw P, Barr P, Varmus H . Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature. 1988; 331(6153):280-3. DOI: 10.1038/331280a0. View

13.

Jacks T, Madhani H, Masiarz F, Varmus H . Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region. Cell. 1988; 55(3):447-58. PMC: 7133365. DOI: 10.1016/0092-8674(88)90031-1. View

14.

Mador N, Panet A, Honigman A . Translation of gag, pro, and pol gene products of human T-cell leukemia virus type 2. J Virol. 1989; 63(5):2400-4. PMC: 250667. DOI: 10.1128/JVI.63.5.2400-2404.1989. View

15.

Jaeger J, Turner D, Zuker M . Improved predictions of secondary structures for RNA. Proc Natl Acad Sci U S A. 1989; 86(20):7706-10. PMC: 298139. DOI: 10.1073/pnas.86.20.7706. View

16.

Reil H, Kollmus H, Weidle U, Hauser H . A heptanucleotide sequence mediates ribosomal frameshifting in mammalian cells. J Virol. 1993; 67(9):5579-84. PMC: 237961. DOI: 10.1128/JVI.67.9.5579-5584.1993. View

17.

Falk H, Mador N, Udi R, Panet A, Honigman A . Two cis-acting signals control ribosomal frameshift between human T-cell leukemia virus type II gag and pro genes. J Virol. 1993; 67(10):6273-7. PMC: 238052. DOI: 10.1128/JVI.67.10.6273-6277.1993. View

18.

Somogyi P, Jenner A, Brierley I, Inglis S . Ribosomal pausing during translation of an RNA pseudoknot. Mol Cell Biol. 1993; 13(11):6931-40. PMC: 364755. DOI: 10.1128/mcb.13.11.6931-6940.1993. View

19.

Dinman J, Wickner R . Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies. Genetics. 1994; 136(1):75-86. PMC: 1205794. DOI: 10.1093/genetics/136.1.75. View

20.

Kollmus H, Honigman A, Panet A, Hauser H . The sequences of and distance between two cis-acting signals determine the efficiency of ribosomal frameshifting in human immunodeficiency virus type 1 and human T-cell leukemia virus type II in vivo. J Virol. 1994; 68(9):6087-91. PMC: 237019. DOI: 10.1128/JVI.68.9.6087-6091.1994. View