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Background
The understanding of the importance of RNA has dramatically changed over recent years. As in the case of proteins, the function of an RNA molecule is encoded in its tertiary structure, which in turn is determined by the molecule's sequence. The prediction of tertiary structures of complex RNAs is still a challenging task.
Results
Using the observation that RNA sequences from the same RNA family fold into conserved structure, we test herein whether parallel modeling of RNA homologs can improve ab initio RNA structure prediction method. EvoClustRNA is a multi-step modeling process, in which homologous sequences for the target sequence are selected using the Rfam database. Subsequently, independent folding simulations using Rosetta FARFAR and SimRNA are carried out. The model of the target sequence is selected based on the most common structural arrangement of the common helical fragments. As a test, on two blind RNA-Puzzles challenges, EvoClustRNA predictions ranked as the first of all submissions for the L-glutamine riboswitch and as the second for the ZMP riboswitch. Moreover, through a benchmark of known structures, we discovered several cases in which particular homologs were unusually amenable to structure recovery in folding simulations compared to the single original target sequence.
Conclusion
This work, for the first time to our knowledge, demonstrates how important is the selection of the target sequence from an alignment of an RNA family for the success of RNA 3D structure prediction. These observations prompt investigations into a new direction of research for checking 3D structure “foldability” or “predictability” of related RNA sequences to obtain accurate predictions. To support new research in this area, we provide all relevant scripts in a documented and ready-to-use form. By exploring new ideas and identification of limitations of the current RNA 3D structure prediction methods, this work is bringing us closer to the near-native computational RNA 3D models.
Keywords
RNA, RNA 3D structure prediction, RNA folding, RNA evolution, Rosetta, SimRNA
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile10.png
- Additionalfile2.FigureS2RelatedtoFig.6.png
- Additionalfile1.FigureS1RelatedtoFig.5.pdf
- Additionalfile9.png
- Additionalfile3.FigureS3.png
- Additionalfile7.alldatarequiredtogeneratedFigure6.xlsx
- Additionalfile6.alldatarequiredtogeneratedFigure5.xlsx
- Additionalfile4.Listofallthesequencesandsecondary.docx
- Additionalfile5.Table1.xlsx
- Additionalfile8.AlldatarequiredtogeneratedFigure7.xlsx
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Bioinformatics.
No community comments so far
Editorial decision: Accept
On 01 Oct, 2019
Editor assigned
On 30 Sep, 2019
Submission checks complete
On 29 Sep, 2019
Editor invited
On 29 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 22 Sep, 2019
Reviewers invited
Invitations sent on 20 Sep, 2019
Reviewer #1 agreed
On 20 Sep, 2019
Review #1 received
Received 20 Sep, 2019
Editor assigned
On 19 Sep, 2019
Submission checks complete
On 18 Sep, 2019
Editor invited
On 18 Sep, 2019
Version 2
Posted 20 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 04 Sep, 2019
Review #1 received
Received 02 Sep, 2019
Reviewers invited
Invitations sent on 23 Aug, 2019
Reviewer #1 agreed
On 23 Aug, 2019
Editor assigned
On 22 Aug, 2019
Submission checks complete
On 21 Aug, 2019
Editor invited
On 21 Aug, 2019
No comments provided
Editorial decision: Major revision
On 22 Jul, 2019
Review #1 received
Received 18 Jul, 2019
Review #2 received
Received 08 Jul, 2019
Reviewer #2 agreed
On 27 Jun, 2019
Editor invited
On 26 Jun, 2019
Editor assigned
On 26 Jun, 2019
Reviewers invited
Invitations sent on 26 Jun, 2019
Reviewer #1 agreed
On 26 Jun, 2019
Submission checks complete
On 25 Jun, 2019
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Bioinformatics.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Bioinformatics.
No community comments so far
Editorial decision: Accept
On 01 Oct, 2019
Editor assigned
On 30 Sep, 2019
Submission checks complete
On 29 Sep, 2019
Editor invited
On 29 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 22 Sep, 2019
Reviewers invited
Invitations sent on 20 Sep, 2019
Reviewer #1 agreed
On 20 Sep, 2019
Review #1 received
Received 20 Sep, 2019
Editor assigned
On 19 Sep, 2019
Submission checks complete
On 18 Sep, 2019
Editor invited
On 18 Sep, 2019
Version 2
Posted 20 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 04 Sep, 2019
Review #1 received
Received 02 Sep, 2019
Reviewers invited
Invitations sent on 23 Aug, 2019
Reviewer #1 agreed
On 23 Aug, 2019
Editor assigned
On 22 Aug, 2019
Submission checks complete
On 21 Aug, 2019
Editor invited
On 21 Aug, 2019
No comments provided
Editorial decision: Major revision
On 22 Jul, 2019
Review #1 received
Received 18 Jul, 2019
Review #2 received
Received 08 Jul, 2019
Reviewer #2 agreed
On 27 Jun, 2019
Editor invited
On 26 Jun, 2019
Editor assigned
On 26 Jun, 2019
Reviewers invited
Invitations sent on 26 Jun, 2019
Reviewer #1 agreed
On 26 Jun, 2019
Submission checks complete
On 25 Jun, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Bioinformatics.
Background
The understanding of the importance of RNA has dramatically changed over recent years. As in the case of proteins, the function of an RNA molecule is encoded in its tertiary structure, which in turn is determined by the molecule's sequence. The prediction of tertiary structures of complex RNAs is still a challenging task.
Results
Using the observation that RNA sequences from the same RNA family fold into conserved structure, we test herein whether parallel modeling of RNA homologs can improve ab initio RNA structure prediction method. EvoClustRNA is a multi-step modeling process, in which homologous sequences for the target sequence are selected using the Rfam database. Subsequently, independent folding simulations using Rosetta FARFAR and SimRNA are carried out. The model of the target sequence is selected based on the most common structural arrangement of the common helical fragments. As a test, on two blind RNA-Puzzles challenges, EvoClustRNA predictions ranked as the first of all submissions for the L-glutamine riboswitch and as the second for the ZMP riboswitch. Moreover, through a benchmark of known structures, we discovered several cases in which particular homologs were unusually amenable to structure recovery in folding simulations compared to the single original target sequence.
Conclusion
This work, for the first time to our knowledge, demonstrates how important is the selection of the target sequence from an alignment of an RNA family for the success of RNA 3D structure prediction. These observations prompt investigations into a new direction of research for checking 3D structure “foldability” or “predictability” of related RNA sequences to obtain accurate predictions. To support new research in this area, we provide all relevant scripts in a documented and ready-to-use form. By exploring new ideas and identification of limitations of the current RNA 3D structure prediction methods, this work is bringing us closer to the near-native computational RNA 3D models.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile10.png
- Additionalfile2.FigureS2RelatedtoFig.6.png
- Additionalfile1.FigureS1RelatedtoFig.5.pdf
- Additionalfile9.png
- Additionalfile3.FigureS3.png
- Additionalfile7.alldatarequiredtogeneratedFigure6.xlsx
- Additionalfile6.alldatarequiredtogeneratedFigure5.xlsx
- Additionalfile4.Listofallthesequencesandsecondary.docx
- Additionalfile5.Table1.xlsx
- Additionalfile8.AlldatarequiredtogeneratedFigure7.xlsx
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