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

Novikova IV, Hennelly SP, Sanbonmatsu KY - Nucleic Acids Res. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

SRAP protein corresponding to coding isoform of SRA. NMR structure of mouse SRAP protein (PDB ID: 2YRU) corresponding to positions 271–609 of SRA RNA transcript. Grey rods, α helices of the protein. Blue spheres, C-α atoms of residues that differ between mouse and human. Bonds representation is used for mutations from mouse to human located in α helices. The majority of mutations occur in linkers connecting helices.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3367176&req=5

gks071-F6: SRAP protein corresponding to coding isoform of SRA. NMR structure of mouse SRAP protein (PDB ID: 2YRU) corresponding to positions 271–609 of SRA RNA transcript. Grey rods, α helices of the protein. Blue spheres, C-α atoms of residues that differ between mouse and human. Bonds representation is used for mutations from mouse to human located in α helices. The majority of mutations occur in linkers connecting helices.

Mentions: With the RNA secondary structure of human SRA (Figure 4) and recent NMR structure of mouse SRA protein (PDB ID: 2YRU), we can simultaneously assess the mutational effects of the SRA gene at the RNA structure and protein structure levels. The solved NMR structure of mouse SRAP contains amino acids corresponding to the positions 93–216 (Figure 6). The IUPred package (66,67) predicts that human SRAP residues 1–90 and 220–236 are highly disordered. We note that while amino acid positions 13–21 (RGWNDPPQF) of SRAP are predicted to be disordered, this region corresponds to the highly structured H2 in Domain I and is highly conserved at the protein and RNA levels.Figure 6.


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

Novikova IV, Hennelly SP, Sanbonmatsu KY - Nucleic Acids Res. (2012)

SRAP protein corresponding to coding isoform of SRA. NMR structure of mouse SRAP protein (PDB ID: 2YRU) corresponding to positions 271–609 of SRA RNA transcript. Grey rods, α helices of the protein. Blue spheres, C-α atoms of residues that differ between mouse and human. Bonds representation is used for mutations from mouse to human located in α helices. The majority of mutations occur in linkers connecting helices.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367176&req=5

gks071-F6: SRAP protein corresponding to coding isoform of SRA. NMR structure of mouse SRAP protein (PDB ID: 2YRU) corresponding to positions 271–609 of SRA RNA transcript. Grey rods, α helices of the protein. Blue spheres, C-α atoms of residues that differ between mouse and human. Bonds representation is used for mutations from mouse to human located in α helices. The majority of mutations occur in linkers connecting helices.
Mentions: With the RNA secondary structure of human SRA (Figure 4) and recent NMR structure of mouse SRA protein (PDB ID: 2YRU), we can simultaneously assess the mutational effects of the SRA gene at the RNA structure and protein structure levels. The solved NMR structure of mouse SRAP contains amino acids corresponding to the positions 93–216 (Figure 6). The IUPred package (66,67) predicts that human SRAP residues 1–90 and 220–236 are highly disordered. We note that while amino acid positions 13–21 (RGWNDPPQF) of SRAP are predicted to be disordered, this region corresponds to the highly structured H2 in Domain I and is highly conserved at the protein and RNA levels.Figure 6.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus