A microRNA feedback loop regulates global microRNA abundance during aging

Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.</jats:p

Application of miRNA-seq in neuropsychiatry: A methodological perspective

MiRNAs are emerging as key molecules to study neuropsychiatric diseases. However, despite the large number of methodologies and software for miRNA-seq analyses, there is little supporting literature for researchers in this area. This review focuses on evaluating how miRNA-seq has been used to study neuropsychiatric diseases to date, analyzing both the main findings discovered and the bioinformatics workflows and tools used from a methodological perspective. The objective of this review is two-fold: first, to evaluate current miRNA-seq procedures used in neuropsychiatry; and second, to offer comprehensive information that can serve as a guide to new researchers in bioinformatics. After conducting a systematic search (from 2016 to June 30, 2020) of articles using miRNA-seq in neuropsychiatry, we have seen that it has already been used for different types of studies in three main categories: diagnosis, prognosis, and mechanism. We carefully analyzed the bioinformatics workflows of each study, observing a high degree of variability with respect to the tools and methods used and several methodological complexities that are identified and discussed in this reviewInstituto de Salud Carlos III | Ref. PI18/01311Ministerio de Economía y Competitividad | Ref. RYC2014-15246Xunta de Galicia | Ref. ED431C2018/55-GR

Specificity Enhancement in microRNA Target Prediction through Knowledge Discovery

Computer Systems, Imagery and Medi

Transcriptome Analysis of Non‐Coding RNAs in Livestock Species: Elucidating the Ambiguity

The recent remarkable development of transcriptomics technologies, especially next generation sequencing technologies, allows deeper exploration of the hidden landscapes of complex traits and creates great opportunities to improve livestock productivity and welfare. Non-coding RNAs (ncRNAs), RNA molecules that are not translated into proteins, are key transcriptional regulators of health and production traits, thus, transcriptomics analyses of ncRNAs are important for a better understanding of the regulatory architecture of livestock phenotypes. In this chapter, we present an overview of common frameworks for generating and processing RNA sequence data to obtain ncRNA transcripts. Then, we review common approaches for analyzing ncRNA transcriptome data and present current state of the art methods for identification of ncRNAs and functional inference of identified ncRNAs, with emphasis on tools for livestock species. We also discuss future challenges and perspectives for ncRNA transcriptome data analysis in livestock species

The transcription factor Foxm1 controls pro-stemness microRNAs in cerebellar neural stem cells (NSCs)

Background: Cerebellar neural stem cells (NSCs) maintenance is of great interest since NSCs can be used to treat impaired cells and tissues or improve regenerative power of degenerating cells in neurodegenerative diseases or spinal cord injuries. Under maintenance conditions, NSCs express a number of Hedgehog-Gli (Hh-Gli) linked and stemness genes (e.g. Nanog, Oct4, Sox2) whose mechanisms of regulation have been under investigation. However, the interplay between transcription factors and microRNAs in NSCs is still being charted. Aim: Identification of new molecular players involved in NSCs’ maintenance with particular interest in the major regulatory pathway Hedgehog-Gli. Materials and Methods: Cells used for the study were NSCs isolated from postnatal day 4 (P4) wild type (C57BL/6) mice cultured both as neurospheres in selective medium and as differentiated NSCs when cultured in medium with serum. NSCs and their differentiated counterparts were analysed by high-throughput technologies. Bioinformatics analysis was used for the identification of the Foxm1-regulated miRNAs; knock-down experiments and clonogenic assays were used for functional studies. Chromatin immunoprecipitation experiments (ChIP) were used to investigate the binding between Foxm1 and its targets and between Foxm1 and its regulators. Results: NSCs and their differentiated counterparts were analysed using next-generation mRNA- and miRNA-sequencing. The transcriptional analysis allowed the identification of Foxm1 as one of the highest transcripts in NSCs and the miRNA-sequencing provided a number of highly expressed miRNAs. The use of bioinformatics analysis resulted in the Foxm1-regulated miRNAs, miR-15 ~ 16 cluster, miR-17 ~ 92 cluster, miR- 130b and miR-301a. Functional experiments, such as knock-down experiments and clonogenic assays enabled the identification of Foxm1 as a downstream mediator of the Hh-Gli signalling and with the ability to regulate the above mention miRNAs. Conclusion: The study presented reveals a new Foxm1-microRNAs network with a major role in the maintenance of NSCs. These results add a previously unidentified important molecular aspect that could be used in future neurodegenerative disease studies, thus enriching the field of translational medicine

Whole transcriptome approach to evaluate the effect of aluminium hydroxide in ovine encephalon

Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences

Whole Transcriptome Approach to Evaluate the Effect of Aluminium Hydroxide in Ovine Encephalon

Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.This work was supported by the Spanish Ministry of Economy grant [MINECO project AGL2013-49137-C3 to BMJ, LL and DA]; University of the Basque Country (UPV/EHU) predoctoral fellowships [PIF15/361 to EV-M and PIF17/306 to MB-A]; and University of the Basque Country (UPV/EHU) postdoctoral fellowship [ESPDOC16/43 to NA]. Thanks to M. Ortega for technical help