PMID- 7882986 OWN - NLM STAT- MEDLINE DCOM- 19950407 LR - 20181113 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 14 IP - 4 DP - 1995 Feb 15 TI - Structural and functional studies of retroviral RNA pseudoknots involved in ribosomal frameshifting: nucleotides at the junction of the two stems are important for efficient ribosomal frameshifting. PG - 842-52 AB - Ribosomal frameshifting, a translational mechanism used during retroviral replication, involves a directed change in reading frame at a specific site at a defined frequency. Such programmed frameshifting at the mouse mammary tumor virus (MMTV) gag-pro shift site requires two mRNA signals: a heptanucleotide shifty sequence and a pseudoknot structure positioned downstream. Using in vitro translation assays and enzymatic and chemical probes for RNA structure, we have defined features of the pseudoknot that promote efficient frameshifting. Heterologous RNA structures, e.g. a hairpin, a tRNA or a synthetic pseudoknot, substituted downstream of the shifty site fail to promote frameshifting, suggesting that specific features of the MMTV pseudoknot are important for function. Site-directed mutations of the MMTV pseudoknot indicate that the pseudoknot junction, including an unpaired adenine nucleotide between the two stems, provides a specific structural determinant for efficient frameshifting. Pseudoknots derived from other retroviruses (i.e. the feline immunodeficiency virus and the simian retrovirus type 1) also promote frameshifting at the MMTV gag-pro shift site, dependent on the same structure at the junction of the two stems. FAU - Chen, X AU - Chen X AD - Department of Chemistry, University of California, Berkeley 94720. FAU - Chamorro, M AU - Chamorro M FAU - Lee, S I AU - Lee SI FAU - Shen, L X AU - Shen LX FAU - Hines, J V AU - Hines JV FAU - Tinoco, I Jr AU - Tinoco I Jr FAU - Varmus, H E AU - Varmus HE LA - eng GR - CA12705/CA/NCI NIH HHS/United States GR - GM10840/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Viral Structural Proteins) RN - 9014-25-9 (RNA, Transfer) SB - IM MH - Animals MH - Base Sequence MH - Cell-Free System MH - Genes, Viral MH - Genes, gag MH - Hydrogen Bonding MH - In Vitro Techniques MH - Mammary Tumor Virus, Mouse/genetics MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Nucleic Acid Conformation MH - *Protein Biosynthesis MH - RNA, Messenger/*metabolism/ultrastructure MH - RNA, Transfer/chemistry MH - RNA, Viral/*metabolism/ultrastructure MH - Rabbits MH - Ribosomes/*metabolism MH - Structure-Activity Relationship MH - Viral Structural Proteins/genetics PMC - PMC398151 EDAT- 1995/02/15 00:00 MHDA- 2001/03/28 10:01 PMCR- 1996/02/15 CRDT- 1995/02/15 00:00 PHST- 1995/02/15 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1995/02/15 00:00 [entrez] PHST- 1996/02/15 00:00 [pmc-release] AID - 10.1002/j.1460-2075.1995.tb07062.x [doi] PST - ppublish SO - EMBO J. 1995 Feb 15;14(4):842-52. doi: 10.1002/j.1460-2075.1995.tb07062.x.