Small regulatory RNAs in mammals

Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
Human Molecular Genetics (Impact Factor: 6.39). 05/2005; 14 Spec No 1(Spec No 1):R121-32. DOI: 10.1093/hmg/ddi101
Source: PubMed


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.


Available from: John S Mattick, Jun 13, 2015
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    • "Nowadays, it is assumed that 98% of the transcribed RNA in humans is not translated into a protein (Mattick & Makunin, 2005). Previously considered to be simply transcriptional junk, these untranslated RNAs (noncoding RNAs, ncRNAs) can have catalytic activity, serve as protein scaffolds, guide the cellular machinery, and are crucial in all aspects of gene expression, such as regulating chromatin remodeling, transcription, and many posttranscriptional events, both in prokaryotes and eukaryotes (Baker, 2011; Guttman & Rinn, 2012; Mattick et al., 2005; Morris & Mattick, 2014; Ponting, Oliver, & Reik, 2009; Storz, Altuvia, & Wassarman, 2005; Wiedenheft, Sternberg, & Doudna, 2012). Some ncRNAs have 100,000 nucleotides such as the long ncRNA Air present in mammals, whereas silencing RNAs may be only 20 nucleotides long (Storz et al., 2005) and are considered as a potential new class of drugs (Fichou & Férec, 2006). "
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    ABSTRACT: Although functional significance of large noncoding RNAs and their complexes with proteins is well recognized, structural information for this class of systems is very scarce. Their inherent flexibility causes problems in crystallographic approaches, while their typical size is beyond the limits of state-of-the-art purely NMR-based approaches. Here, we review an approach that combines high-resolution NMR restraints with lower resolution long-range constraints based on site-directed spin labeling and measurements of distance distribution restraints in the range between 15 and 80Å by the four-pulse double electron-electron resonance (DEER) EPR technique. We discuss sample preparation, the basic assumptions behind data analysis in the EPR-based distance measurements, treatment of the label-based constraints in generation of the structure, and the back-calculation of distance distributions for structure validation. Step-by-step protocols are provided for DEER distance distribution measurements including data analysis and for CYANA based structure calculation using combined NMR and EPR data. © 2015 Elsevier Inc. All rights reserved.
    Methods in enzymology 06/2015; 558(1):279-331. DOI:10.1016/bs.mie.2015.02.005 · 2.09 Impact Factor
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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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    • "The majority of the human genome is transcribed but not translated. Such RNAs are classified as long non-coding RNAs (lncRNAs) when longer than 200 nucleotides [73-75]. To date, relatively few lncRNAs have been functionally characterized, but increasing evidence suggests that many may have important functions, including the regulation of transcription, RNA processing and translation, DNA methylation, and chromatin architecture, both locally (cis-acting) and across some genomic distance (trans-acting) [76-78]. "
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    ABSTRACT: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset inherited neurodegenerative disorder characterized by intentional tremor, gait ataxia, autonomic dysfunction, and cognitive decline. FXTAS is caused by the presence of a long CGG repeat tract in the 5' UTR of the FMR1 gene. In contrast to Fragile X syndrome, in which the FMR1 gene harbors over 200 CGG repeats but is transcriptionally silent, the clinical features of FXTAS arise from a toxic gain of function of the elevated levels of FMR1 transcript containing the long CGG tract. However, how this RNA leads to neuronal cell dysfunction is unknown. Here, we discuss the latest advances in the current understanding of the possible molecular basis of FXTAS.
    Journal of Neurodevelopmental Disorders 07/2014; 6(1):23. DOI:10.1186/1866-1955-6-23 · 3.27 Impact Factor
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