RNA Editing Therapeutics: Advances, Challenges and Perspectives on Combating Heart Disease.

Cardiovascular disease still remains the leading cause of morbidity and mortality worldwide. Current pharmacological or interventional treatments help to tackle symptoms and even reduce mortality, but cardiovascular disease cases continue to rise. The emergence of novel therapeutic strategies that precisely and efficiently combat cardiovascular disease is therefore deemed more essential than ever. RNA editing, the cell-intrinsic deamination of adenosine or cytidine RNA residues, changes the molecular identity of edited nucleotides, severely altering the fate of RNA molecules involved in key biological processes. The most common type of RNA editing is the deamination of adenosine residue to inosine (A-to-I), which is catalysed by adenosine deaminases acting on RNA (ADARs). Recent efforts have convincingly liaised RNA editing-based mechanisms to the pathophysiology of the cardiovascular system. In this review, we will briefly introduce the basic concepts of the RNA editing field of research. We will particularly focus our discussion on the therapeutic exploitation of RNA editing as a novel therapeutic tool as well as the future perspectives for its use in cardiovascular disease treatment.

The embryonic transcriptome of Parhyale hawaiensis reveals different dynamics of microRNAs and mRNAs during the maternal-zygotic transition.

Parhyale hawaiensis has emerged as the crustacean model of choice due to its tractability, ease of imaging, sequenced genome, and development of CRISPR/Cas9 genome editing tools. However, transcriptomic datasets spanning embryonic development are lacking, and there is almost no annotation of non-protein-coding RNAs, including microRNAs. We have sequenced microRNAs, together with mRNAs and long non-coding RNAs, in Parhyale using paired size-selected RNA-seq libraries at seven time-points covering important transitions in embryonic development. Focussing on microRNAs, we annotate 175 loci in Parhyale, 88 of which have no known homologs. We use these data to annotate the microRNAome of 37 crustacean genomes, and suggest a core crustacean microRNA set of around 61 sequence families. We examine the dynamic expression of microRNAs and mRNAs during the maternal-zygotic transition. Our data suggest that zygotic genome activation occurs in two waves in Parhyale with microRNAs transcribed almost exclusively in the second wave. Contrary to findings in other arthropods, we do not predict a general role for microRNAs in clearing maternal transcripts. These data significantly expand the available transcriptomics resources for Parhyale, and facilitate its use as a model organism for the study of small RNAs in processes ranging from embryonic development to regeneration.

miRBase: from microRNA sequences to function.

miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We describe improvements to the database and website to provide more information about the quality of microRNA gene annotations, and the cellular functions of their products. We have collected 1493 small RNA deep sequencing datasets and mapped a total of 5.5 billion reads to microRNA sequences. The read mapping patterns provide strong support for the validity of between 20% and 65% of microRNA annotations in different well-studied animal genomes, and evidence for the removal of >200 sequences from the database. To improve the availability of microRNA functional information, we are disseminating Gene Ontology terms annotated against miRBase sequences. We have also used a text-mining approach to search for microRNA gene names in the full-text of open access articles. Over 500 000 sentences from 18 542 papers contain microRNA names. We score these sentences for functional information and link them with 12 519 microRNA entries. The sentences themselves, and word clouds built from them, provide effective summaries of the functional information about specific microRNAs. miRBase is publicly and freely available at http://mirbase.org/.