Control of gene expression in bacteriophage P22 by a small antisense RNA. II. Characterization of mutants defective in repression.

Wu, Teresa; Liao, Sha-Mei; McClure, William R.; Susskind, Miriam M.

doi:10.1101/gad.1.2.204

Cited by 36 publications

(12 citation statements)

References 41 publications

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“…As demonstrated by ADO1͞STR10, ADO2͞STR7, and ADO3͞STR11 (Fig. 3), initial oligonucleotide contacts require short linear regions adjacent to, or between structures (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

Lanz

Razani²,

Goldberg³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

154

151

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Steroid receptor RNA activator (SRA) is an RNA transcript that functions as a eukaryotic transcriptional coactivator for steroid hormone receptors. We report here the isolation and functional characterization of distinct RNA substructures within the SRA molecule that constitute its coactivation function. We used comparative sequence analysis and free energy calculations to systematically study SRA RNA subdomains for identification of structured regions and base pairings, and we used site-directed mutagenesis to assess their functional consequences. Together with genetic deletion analysis, this approach identified six RNA motifs in SRA important for coactivation. Because all nucleotide changes in the mutants that disrupted SRA function were silent mutations presumed not to alter deduced encoded amino acid sequence, our analysis provides strong evidence that SRA-mediated coactivation is executed by distinct RNA motifs and not by an encoded protein.N uclear receptors play critical roles in eukaryotic development, metabolism, reproduction, and disease through regulation of gene expression (1, 2). Recent advances in transcription have suggested that nuclear receptors form large, multicomponent complexes with coactivators and corepressors at the enhancer and promoter regions of target genes (3, 4). These complexes include factors exerting different enzymatic functions such as chromatin remodeling activities, and a variety of combinations of coregulators are believed to be essential for regulated gene expression.We have previously reported the isolation and functional characterization of a novel transcriptional coactivator termed SRA (steroid receptor RNA activator; ref. 5). SRA acts as a catalytic RNA transcript by regulating eukaryotic gene expression mediated by the steroid receptors (SRs). When overexpressed in mammalian cells, recombinant SRA showed potent coactivation activity with the receptors for androgens, estrogens, glucocorticoids, and progestins (PR). We showed that several isoforms of SRA exist, and we grouped them into three splice classes based on their sequences outside a common core region. The SRA sequences of all of our cDNA clones contain an ORF but are devoid of an initiation ATG. Although the existence of a translation product of SRA cannot be categorically excluded, we have provided evidence to indicate that SRA functions as an RNA transcript (5).Because the function of an RNA can be best understood in terms of its secondary or tertiary structure, we wished to further define the coactivation function we previously observed in SRA by using low-resolution RNA structure modeling. RNA secondary structure is a composite of hydrogen bonds between bases allowing certain noncanonical pairings, forming structures with double-helical motifs, bulges, bubbles, and loops that then spatially arrange to assemble specific intra-and intermolecular interactions. By using comparative sequence analysis and lowresolution RNA modeling, we set out to predict functional substructures of SRA and to obtain a framework wi...

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“…As demonstrated by ADO1͞STR10, ADO2͞STR7, and ADO3͞STR11 (Fig. 3), initial oligonucleotide contacts require short linear regions adjacent to, or between structures (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

Lanz

Razani²,

Goldberg³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

154

151

View full text Add to dashboard Cite

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“…The first of these to be discovered was the P22 antirepressor (Ant), which binds to repressor and causes it to release repression (Susskind and Botstein, 1975). Transcription of the ant gene in a prophage is kept off by two additional phage-encoded repressors, Mnt and Arc, and a small antisense RNA, Sar, that controls the translation of ant mRNA (Prell and Harvey, 1983; Liao et al , 1987; Wu et al , 1987; Schaefer and McClure, 1997). Salmonella lambdoid phage gifsy-1 encodes an antirepressor GfoR that is repressed by the host LexA repressor (Lemire et al , 2011).…”

Section: Historical Importance and Recent Progressmentioning

confidence: 99%

Bacteriophage lambda: Early pioneer and still relevant

2015

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Molecular genetic research on bacteriophage lambda carried out during its golden age from the mid 1950's to mid 1980's was critically important in the attainment of our current understanding of the sophisticated and complex mechanisms by which the expression of genes is controlled, of DNA virus assembly and of the molecular nature of lysogeny. The development of molecular cloning techniques, ironically instigated largely by phage lambda researchers, allowed many phage workers to switch their efforts to other biological systems. Nonetheless, since that time the ongoing study of lambda and its relatives have continued to give important new insights. In this review we give some relevant early history and describe recent developments in understanding the molecular biology of lambda's life cycle.

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“…A few years later, the 70 nucleotide RNA-OUT of the transposon Tn 10 was found to affect transposition by repressing transposase synthesis (95). In addition, the ~ 70 nucleotide Sar RNA of bacteriophage P22 (54, 119) and the 77 nucleotide OOP RNA of bacteriophage λ (50) were reported to repress synthesis of the Ant and cII phage proteins, respectively. Another type of plasmid antisense RNA discovered early on was the ~70 nucleotide Sok RNA of plasmid R1, which represses synthesis of the toxic Hok protein responsible for postsegregational killing of cells when the R1 plasmid is lost (24).…”

Section: Introductionmentioning

confidence: 99%

Bacterial Antisense RNAs: How Many Are There, and What Are They Doing?

2010

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Antisense RNAs encoded on the DNA strand opposite another gene have the potential to form extensive base pairing interactions with the corresponding sense RNA. Unlike other smaller regulatory RNAs in bacteria, antisense RNAs range in size, from tens to thousands of nucleotides. The numbers of antisense RNAs reported for different bacteria vary extensively but hundreds have been suggested in some species. If all of these reported antisense RNAs are expressed at levels sufficient to regulate the genes encoded opposite them, antisense RNAs could significantly impact gene expression in bacteria. Here we review the evidence for these RNA regulators and describe what is known about the functions and mechanisms of action for some of these RNAs. Important considerations for future research as well as potential applications are also discussed.

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Control of gene expression in bacteriophage P22 by a small antisense RNA. II. Characterization of mutants defective in repression.

Cited by 36 publications

References 41 publications

Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

Bacteriophage lambda: Early pioneer and still relevant

Bacterial Antisense RNAs: How Many Are There, and What Are They Doing?

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