Small regulatory RNAs in mammals

Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Human Molecular Genetics (Impact Factor: 6.68). 05/2005; 14 Spec No 1(Spec No 1):R121-32. DOI: 10.1093/hmg/ddi101
Source: PubMed

ABSTRACT Mammalian cells harbor numerous small non-protein-coding RNAs, including small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), short interfering RNAs (siRNAs) and small double-stranded RNAs, which regulate gene expression at many levels including chromatin architecture, RNA editing, RNA stability, translation, and quite possibly transcription and splicing. These RNAs are processed by multistep pathways from the introns and exons of longer primary transcripts, including protein-coding transcripts. Most show distinctive temporal- and tissue-specific expression patterns in different tissues, including embryonal stem cells and the brain, and some are imprinted. Small RNAs control a wide range of developmental and physiological pathways in animals, including hematopoietic differentiation, adipocyte differentiation and insulin secretion in mammals, and have been shown to be perturbed in cancer and other diseases. The extent of transcription of non-coding sequences and the abundance of small RNAs suggests the existence of an extensive regulatory network on the basis of RNA signaling which may underpin the development and much of the phenotypic variation in mammals and other complex organisms and which may have different genetic signatures from sequences encoding proteins.

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Available from: John S Mattick, Jun 13, 2015
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    • "Recently, emerging evidence has pointed to an important role of RNAs, particularly non-protein coding RNAs (ncRNA) in controlling multiple epigenetic phenomena such as X-chromosome inactivation, gene imprinting and RNAi-mediated silencing (Bernstein and Allis, 2005; Mattick and Makunin, 2006). The sizes of ncRNAs range from 21 nucleotides (nt), as in the case of mature microRNAs (miRNAs), to more than 100,000 nt, such as the Air (antisense to Igf2r) RNA (Lyle et al., 2000; Storz, 2002; Bartel, 2004; Mattick and Makunin, 2005; Cao et al., 2006). Several distinct classes of ncRNAs, such as small nucleolar RNA (snoRNA), microRNA (miRNA) and long ncRNA (lncRNA), have been found highly expressed in the nervous system (Cao et al., 2006; Mehler and Mattick, 2006, 2007; Mehler, 2008). "
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    • "These findings officially started a new field of investigation in small ncRNAs, more specifically, miRNAs. Currently, the existence of miRNAs has been extensively shown in insects and mammals (Ambros, 2001; Ambros et al., 2003; Lagos-Quintana et al., 2003; Mattick and Makunin, 2005), and the database of miRNAs has registered approximately 25,000 sequences found in 32 organisms representing vertebrates, invertebrates, plants and viruses ( "
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    ABSTRACT: One of the major developments that resulted from the human genome sequencing projects was a better understanding of the role of non-coding RNAs (ncRNAs). NcRNAs are divided into several different categories according to size and function; however, one shared feature is that they are not translated into proteins. In this review, we will discuss relevant aspects of ncRNAs, focusing on two main types: i) microRNAs, which negatively regulate gene expression either by translational repression or target mRNA degradation, and ii) small interfering RNAs (siRNAs), which are involved in the biological process of RNA interference (RNAi). Our knowledge regarding these two types of ncRNAs has increased dramatically over the past decade, and they have a great potential to become therapeutic alternatives for a variety of human conditions.
    Genetics and Molecular Biology 03/2014; 37(1 Suppl):285-293. DOI:10.1590/S1415-47572014000200014 · 0.88 Impact Factor
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    • "Although evidence for all three hypotheses has been demonstrated using coding genes in Drosophila (Parisi et al. 2003; Hense et al. 2007; Vibranovski et al. 2009a, Bachtrog et al. 2010; Kemkemer et al. 2011, 2013), no systematic experimental study on noncoding RNAs has been done so far to test these hypotheses. Noncoding RNAs (ncRNAs) play important roles in many reproductive processes (Mattick and Makunin 2005; Prasanth and Spector 2007). If selection governs the chromosomal distribution of sex-biased genes, we expect male-biased ncRNAs to exhibit a chromosomal distribution similar to that observed for coding genes. "
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    ABSTRACT: Recent studies revealed key roles of non-coding RNAs in sex-related pathways, but little is known about the evolutionary forces acting on these non-coding RNAs. Profiling the transcriptome of Drosophila melanogaster with whole-genome tiling arrays found that 15% of male-biased transcribed fragments (transfrags) are intergenic non-coding RNAs (incRNAs), suggesting a potentially important role for incRNAs in sex-related biological processes. Statistical analysis revealed a paucity of male-biased incRNAs and coding genes on the X chromosome, suggesting that similar evolutionary forces could be affecting the genomic organization of both coding and non-coding genes. Expression profiling across germline and somatic tissues further suggested that both male meiotic sex chromosome inactivation (MSCI) and sexual antagonism could contribute to the chromosomal distribution of male-biased incRNAs. Comparative sequence analysis showed that the evolutionary age of male-biased incRNAs is a significant predictor of their chromosomal locations. In addition to identifying abundant sex-biased incRNAs in fly genome, our work unveils a global picture of the complex interplay between non-coding RNAs and sexual chromosome evolution.
    Genome Research 01/2014; 24(4). DOI:10.1101/gr.165837.113 · 13.85 Impact Factor
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