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      Using miRNAs as diagnostic biomarkers for male infertility: opportunities and challenges

      Author(s): 1 , 1
      Publication date Created:
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      Journal: Molecular Human Reproduction
      Publisher: Oxford University Press (OUP)

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          Abstract

          The non-coding genome has been extensively studied for its role in human development and diseases. MicroRNAs (miRNAs) are small non-coding RNAs, which can regulate the expression of hundreds of genes at the post-transcriptional level. Therefore, any defects in miRNA biogenesis or processing can affect the genes and have been linked to several diseases. Male infertility is a clinical disorder with a significant number of cases being idiopathic. Problems in spermatogenesis and epididymal maturation, testicular development, sperm maturation or migration contribute to male infertility, and many of these idiopathic cases are related to issues with the miRNAs which tightly regulate these processes. This review summarizes the recent research on various such miRNAs and puts together the candidate miRNAs that may be used as biomarkers for diagnosis. The development of strategies for male infertility treatment using anti-miRs or miRNA mimics is also discussed. Although promising, the development of miRNA diagnostics and therapeutics is challenging, and ways to overcome some of these challenges are also reviewed.

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)
          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
          Article 0 comments Cited 2488 times – based on 0 reviews     Review now
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            MicroRNAs: target recognition and regulatory functions.

            David Bartel (2009)
            MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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              Most mammalian mRNAs are conserved targets of microRNAs.

              Robin C. Friedman, Kyle Farh, Christopher Burge … (2009)
              MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2-7), particularly those in 3' untranslated regions (3'UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the "offset 6mer," to be detected. In total, >45,000 miRNA target sites within human 3'UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3' end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (P(CT)) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3'-compensatory sites), are available at the TargetScan website, which displays the P(CT) for each site and each predicted target.
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                Author and article information

                Contributors
                Journal
                Title: Molecular Human Reproduction
                Publisher: Oxford University Press (OUP)
                ISSN (Electronic): 1460-2407
                Publication date Created: April 2020
                Publication date Created: April 24 2020
                Publication date Created: February 21 2020
                Publication date Other: April 2020
                Publication date (Print): April 24 2020
                Publication date (Electronic): February 21 2020
                Volume: 26
                Issue: 4
                Pages: 199-214
                Affiliations
                [1 ]Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab 143005 India
                Article
                DOI: 10.1093/molehr/gaaa016
                PubMed ID: 32084276
                SO-VID: 120f7e40-4931-4313-a7be-3e3b3a85012d
                Copyright © © 2020
                License:

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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