Special Issue "Computational Analysis of RNA Structure and Function"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Technologies and Resources for Genetics".

Deadline for manuscript submissions: 30 April 2018

Special Issue Editor

Guest Editor
Prof. Dr. Jan Gorodkin

Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Special Issue Information

Dear Colleagues,

RNA, the matter of transcripts, is being intensively studied across all living organisms in numerous ways, ranging from analysis of its structure and folding properties to high-throughput sequencing (HTS) and its applications, including those targeting interactions and structure itself. Indeed, RNA often folds into complex structures central to its function by, which, for example, function through binding to other RNAs and proteins. Hence, the relevance of predicting both RNA structure and RNA interactions does not only concern structure determination of single sequences, but do also addresses analysis of large-scale data sets. Efficient algorithms and implementations are also essential to meet the demand of large-scale applications. Another challenge is that algorithms for RNA structure and interaction analysis are relatively computational expensive, for example when compared to their counterpart of sequence alignments. Furthermore, the vast majority of trait and disease related mutations in higher eukaryotes are located in non-coding regions of the genome and since most of the genome is transcribed into RNA, the mutations hold the potential impact structure and thereby function of the RNA molecules. This Special Issue includes computational strategies for analysis of RNA structure and function covering both algorithmic aspects, as well as bioinformatic analysis large-scale related data sets.

Prof. Dr. Jan Gorodkin
Guest Editor

Manuscript Submission Information

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  • RNA structure (2D and 3D)
  • RNA folding and dynamics
  • RNA interactions
  • Comparative structure analysis
  • Analysis of large scale data sets related to RNA structure
  • RNA structure and mutations
  • RNA modification
  • RNA structure and expression

Published Papers

This special issue is now open for submission, see below for planned papers.

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Tentative title: Mutually exclusive exon clusters originate through tandem exon duplications by a mechanism that creates competing RNA structures

Author: Dmitri D. Pervouchine

Affiliation: Skolkovo Institute for Science and Technology, Moscow, Russia

Tentative abstract: Alternative splicing is a commonly used mechanism of diversifying protein products produced from the same locus. One particular type of alternative splicing is mutually exclusive exons (MXE), in which one and only one exon from an array is included in the mature transcript. A number of genes in Drosophilids that contain MXE (e.g. dscam, mrp, srp) do so by using a splicing mechanism that is dependent on RNA structure. Their transcripts contain multiple sites called selector sequences which are all complementary to a regulatory element called docking site; only one of the competing base pairings can form at a time, which leads to mutually exclusive exon choice.  A class of MXE that tend to have similar lengths and sequence content are believed to originate through tandem genomic duplications. Here we study in detail these MXE classes in different clades and find evidence for the evolutionary mechanism that generates competing RNA structures. Namely, we show that tandem duplications likely affect introns andduplicate one of the two complementary motifs which loop-out the exon. This generates multiple selector sequences that compete for the same docking site, a pattern that is consistent with the arrangement of MXE throughout the gene. These results suggest that the role of competing RNA structures in eukaryotic transcript processing is more widespread than it is believed currently.


Tentative title: The role of long-range base-pairings in the processing of eukaryotic transcripts

Author: Dmitri D. Pervouchine

Affiliation: Skolkovo Institute for Science and Technology, Moscow, Russia

Tentative abstract: RNA structure is commonly viewed as comprising two levels, the local secondary structure which is formed by proximate regions in the primary sequence, and the global structure which also includes long-range interactions. Computational methods can predict RNA secondary structure reasonably well for short molecules, but predicting long-range interactions and the global structure of long RNAs is currently not feasible. The regulatory role of secondary structure is well-studied in prokaryotes and many important mechanisms are already known (e.g., riboswitches, attenuators, etc), while eukaryotic transcripts largely remain terra incognita from the structural point of view because of their length. In this review I will discuss known long-range RNA structures in eukaryotic genes, classify their mechanisms of action, and assemble a unified view of the role played by long-range base-pairings in the processing of eukaryotic transcripts. 


Tentative title: Structure and evolution of tracrRNAs in Class 2 CRISPR-Cas systems

Authors: Guilhem Faure, Sergey Shmakov, Kira S. Makarova, Yuri I. Wolf, Eugene V. Koonin*

Affiliations: National Center for Biotechnology Information, National  Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA

Tentative abstract: The CRISPR-Cas systems belong to two classes, with multi-subunit effector complexes in Class 1, and single multi-domain protein effectors in Class 2. The latter encompasses types II, V and VI that differ primarily by the domain architectures of the effector proteins. In all type II systems as well as subtype V-B, maturation of the precursor crRNA (pre-crRNA) requires a trans-acting CRISPR (tracr) RNA whereas in subtype V-A and type VI, no tracrRNA has been identified. In Cas9-CRISPR technologies, tracrRNA is artificially fused to crRNA to form a single-guide RNA. The tracrRNA consists of a portion complementary to the direct repeat from the corresponding CRISPR array and a unique portion. The origin and evolution of tracrRNA remain open problems which we sought to investigate by comparative analysis of co-folding between tracrRNA and crRNA. By comparing the available structures of Class 2 effectors complexed with the crRNA, tracrRNA (where involved) and the target, we identified the nexus structure of the tracrRNA in types II-A and II-B and a similar local fold in type V-B, where it involves both tracrRNA and the repeat portion of the crRNA, and in subtype V-A, where it is formed by the repeat alone. This observation suggests an important function of the nexus structure that is common to all type II and type V systems but could have evolved convergently, involving tracrRNA alone, the tracrRNA-repeat hybrid or the repeat alone. Using a larger set of tracrRNA-repeat pairs representative of the diversity of type II systems, we predicted the structures of each crRNA-tracrRNA co-folding and identified the nexus structure in almost all of them. The nexus is almost always located 2 to 3 nucleotides away from the tracrRNA-repeat hybrid region. We also observed that the 5’-terminal base of the repeat is always paired with the tracrRNA. We propose that the role of the nexus structure is to prevent base-pairing between tracrRNA and the spacer whereas the pairing of the 5' base of the repeat prevents interaction between the repeat and the DNA target. Thus, both features appear to ensure full availability of the spacer to interact specifically and completely with the DNA target. We investigated the origins of tracrRNA by tracing the coevolution of the tracrRNA and the corresponding repeats using simulated and ancestral RNA guide sequences, and observed a conservation of optimal hybrid energy that corresponds to partial, rather than complete, base-pairing. Then, we analyzed the tracrRNA in microbial genomes and found that tracrRNAs located close to CRISPR arrays are expressed from the same strand and downstream of the CRISPR array, and can even overlap with the array. We propose an evolutionary model in which tracrRNA emerges from the distal decaying repeat of the CRISPR array.

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