Genomic screening of fish-specific genes in gnathostomes and their functions in fin development.

In this study, we comprehensively searched for fish-specific genes in gnathostomes that contribute to development of the fin, a fish-specific trait. Many previous reports suggested that animal group-specific genes are often important for group-specific traits. Clarifying the roles of fish-specific genes in fin development of gnathostomes, for example, can help elucidate the mechanisms underlying the formation of this trait.

Web Services for RNA-RNA Interaction Prediction.

Non-coding RNAs have various biological functions such as translational regulation, and RNA-RNA interactions play essential roles in the mechanisms of action of these RNAs. Therefore, RNA-RNA interaction prediction is an important problem in bioinformatics, and many tools have been developed for the computational prediction of RNA-RNA interactions. In addition to the development of novel algorithms with high accuracy, the development and maintenance of web services is essential for enhancing usability by experimental biologists.

Remarkable improvement in detection of readthrough downstream-of-gene transcripts by semi-extractable RNA-sequencing.

The mammalian cell nucleus contains dozens of membrane-less nuclear bodies that play significant roles in various aspects of gene expression. Several nuclear bodies are nucleated by specific architectural noncoding RNAs (arcRNAs) acting as structural scaffolds. We have reported that a minor population of cellular RNAs exhibits an unusual semi-extractable feature upon using the conventional procedure of RNA preparation and that needle shearing or heating of cell lysates remarkably improves extraction of dozens of RNAs.

DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells.

Myeloid malignancies with DDX41 mutations are often associated with bone marrow failure and cytopenia before overt disease manifestation. However, the mechanisms underlying these specific conditions remain elusive. Here, we demonstrate that loss of DDX41 function impairs efficient RNA splicing, resulting in DNA replication stress with excess R-loop formation.

Extended ensemble simulations of a SARS-CoV-2 nsp1-5'-UTR complex.

Nonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 180-residue protein that blocks translation of host mRNAs in SARS-CoV-2-infected cells. Although it is known that SARS-CoV-2's own RNA evades nsp1's host translation shutoff, the molecular mechanism underlying the evasion was poorly understood. We performed an extended ensemble molecular dynamics simulation to investigate the mechanism of the viral RNA evasion.

m A modification of HSATIII lncRNAs regulates temperature-dependent splicing.

Nuclear stress bodies (nSBs) are nuclear membraneless organelles formed around stress-inducible HSATIII architectural long noncoding RNAs (lncRNAs). nSBs repress splicing of hundreds of introns during thermal stress recovery, which are partly regulated by CLK1 kinase phosphorylation of temperature-dependent Ser/Arg-rich splicing factors (SRSFs). Here, we report a distinct mechanism for this splicing repression through protein sequestration by nSBs.

MeCP2 Levels Regulate the 3D Structure of Heterochromatic Foci in Mouse Neurons.

Methyl-CpG binding protein 2 (MeCP2) is a nuclear protein critical for normal brain function, and both depletion and overexpression of MeCP2 lead to severe neurodevelopmental disease, Rett syndrome (RTT) and multiplication disorder, respectively. However, the molecular mechanism by which abnormal MeCP2 dosage causes neuronal dysfunction remains unclear. As MeCP2 expression is nearly equivalent to that of core histones and because it binds DNA throughout the genome, one possible function of MeCP2 is to regulate the 3D structure of chromatin.

Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters.

Can current simulations quantitatively predict the stability of ribonucleic acids (RNAs)? In this research, we apply a free-energy perturbation simulation of RNAs containing inosine, a modified ribonucleic base, to the derivation of RNA nearest-neighbor parameters. A parameter set derived solely from 30 simulations was used to predict the free-energy difference of the RNA duplex with a mean unbiased error of 0.70 kcal/mol, which is a level of accuracy comparable to that obtained with parameters derived from 25 experiments.

Finding the direct optimal RNA barrier energy and improving pathways with an arbitrary energy model.

Motivation: RNA folding kinetics plays an important role in the biological functions of RNA molecules. An important goal in the investigation of the kinetic behavior of RNAs is to find the folding pathway with the lowest energy barrier. For this purpose, most of the existing methods use heuristics because the number of possible pathways is huge even if only the shortest (direct) folding pathways are considered.

RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

Background: Analysis of secondary structures is essential for understanding the functions of RNAs. Because RNA molecules thermally fluctuate, it is necessary to analyze the probability distributions of their secondary structures. Existing methods, however, are not applicable to long RNAs owing to their high computational complexity.

LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.

A number of long noncoding RNAs (lncRNAs) are induced in response to specific stresses to construct membrane-less nuclear bodies; however, their function remains poorly understood. Here, we report the role of nuclear stress bodies (nSBs) formed on highly repetitive satellite III (HSATIII) lncRNAs derived from primate-specific satellite III repeats upon thermal stress exposure. A transcriptomic analysis revealed that depletion of HSATIII lncRNAs, resulting in elimination of nSBs, promoted splicing of 533 retained introns during thermal stress recovery.

LncRRIsearch: A Web Server for lncRNA-RNA Interaction Prediction Integrated With Tissue-Specific Expression and Subcellular Localization Data.

Long non-coding RNAs (lncRNAs) play critical roles in various biological processes, but the function of the majority of lncRNAs is still unclear. One approach for estimating a function of a lncRNA is the identification of its interaction target because functions of lncRNAs are expressed through interaction with other biomolecules in quite a few cases. In this paper, we developed "LncRRIsearch," which is a web server for comprehensive prediction of human and mouse lncRNA-lncRNA and lncRNA-mRNA interaction.

reactIDR: evaluation of the statistical reproducibility of high-throughput structural analyses towards a robust RNA structure prediction.

Background: Recently, next-generation sequencing techniques have been applied for the detection of RNA secondary structures, which is referred to as high-throughput RNA structural (HTS) analyses, and many different protocols have been used to detect comprehensive RNA structures at single-nucleotide resolution. However, the existing computational analyses heavily depend on the experimental methodology to generate data, which results in difficulties associated with statistically sound comparisons or combining the results obtained using different HTS methods.

Results: Here, we introduced a statistical framework, reactIDR, which can be applied to the experimental data obtained using multiple HTS methodologies.

Identification of Transposable Elements Contributing to Tissue-Specific Expression of Long Non-Coding RNAs.

It has been recently suggested that transposable elements (TEs) are re-used as functional elements of long non-coding RNAs (lncRNAs). This is supported by some examples such as the human endogenous retrovirus subfamily H (HERVH) elements contained within lncRNAs and expressed specifically in human embryonic stem cells (hESCs), as required to maintain hESC identity. There are at least two unanswered questions about all lncRNAs.

Computational prediction of lncRNA-mRNA interactionsby integrating tissue specificity in human transcriptome.

Unlabelled: Long noncoding RNAs (lncRNAs) play a key role in normal tissue differentiation and cancer development through their tissue-specific expression in the human transcriptome. Recent investigations of macromolecular interactions have shown that tissue-specific lncRNAs form base-pairing interactions with various mRNAs associated with tissue-differentiation, suggesting that tissue specificity is an important factor controlling human lncRNA-mRNA interactions.Here, we report investigations of the tissue specificities of lncRNAs and mRNAs by using RNA-seq data across various human tissues as well as computational predictions of tissue-specific lncRNA-mRNA interactions inferred by integrating the tissue specificity of lncRNAs and mRNAs into our comprehensive prediction of human lncRNA-RNA interactions.

Improved Accuracy in RNA-Protein Rigid Body Docking by Incorporating Force Field for Molecular Dynamics Simulation into the Scoring Function.

RNA-protein interactions play fundamental roles in many biological processes. To understand these interactions, it is necessary to know the three-dimensional structures of RNA-protein complexes. However, determining the tertiary structure of these complexes is often difficult, suggesting that an accurate rigid body docking for RNA-protein complexes is needed.

Comprehensive prediction of lncRNA-RNA interactions in human transcriptome.

Motivation: Recent studies have revealed that large numbers of non-coding RNAs are transcribed in humans, but only a few of them have been identified with their functions. Identification of the interaction target RNAs of the non-coding RNAs is an important step in predicting their functions. The current experimental methods to identify RNA-RNA interactions, however, are not fast enough to apply to a whole human transcriptome.

Bioinformatics tools for lncRNA research.

Current experimental methods to identify the functions of a large number of the candidates of long non-coding RNAs (lncRNAs) are limited in their throughput. Therefore, it is essential to know which tools are effective for understanding lncRNAs so that reasonable speed and accuracy can be achieved. In this paper, we review the currently available bioinformatics tools and databases that are useful for finding non-coding RNAs and analyzing their structures, conservation, interactions, co-expressions and localization.

Analysis of base-pairing probabilities of RNA molecules involved in protein-RNA interactions.

Motivation: Understanding the details of protein-RNA interactions is important to reveal the functions of both the RNAs and the proteins. In these interactions, the secondary structures of the RNAs play an important role. Because RNA secondary structures in protein-RNA complexes are variable, considering the ensemble of RNA secondary structures is a useful approach.

Dissecting the protein-RNA interface: the role of protein surface shapes and RNA secondary structures in protein-RNA recognition.

Protein-RNA interactions are essential for many biological processes. However, the structural mechanisms underlying these interactions are not fully understood. Here, we analyzed the protein surface shape (dented, intermediate or protruded) and the RNA base pairing properties (paired or unpaired nucleotides) at the interfaces of 91 protein-RNA complexes derived from the Protein Data Bank.