Structural architecture of the human long non-coding RNA, steroid receptor RNA activator

While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a...

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Vydané v:Nucleic acids research Ročník 40; číslo 11; s. 5034 - 5051
Hlavní autori: Novikova, Irina V., Hennelly, Scott P., Sanbonmatsu, Karissa Y.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Oxford University Press 01.06.2012
Predmet:
Alternative splicing
Amino Acid Sequence
Animals
Base Sequence
BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Breast cancer
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Coevolution
Conserved Sequence
Evolution
Evolution, Molecular
Humans
Mice
Molecular modelling
Molecular Sequence Data
Mutation
non-coding RNA
Nucleic Acid Conformation
Nucleotide sequence
Nucleotides - chemistry
Protein structure
Ribonuclease
Ribonucleases
RNA
RNA, Long Noncoding
RNA, Untranslated - chemistry
Secondary structure
Sequence Alignment
Sex hormones
Steroid hormone receptors
Translation
ISSN:0305-1048, 1362-4962, 1362-4962
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Popis
Shrnutí:While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of SRA are also expressed to produce proteins, making the SRA gene a unique bifunctional system. Our experimental findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the SRA gene at the RNA structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of RNA structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the RNA structural core rather than its translational product. We perform similar experiments on alternatively spliced SRA isoforms to assess their structural features.
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AC52-06NA25396
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gks071