Saturday, 22 December 2012


Non-coding RNAs in human disease by Esteller
Types of ncRNAs and their functions
lnc RNAs are ncRNAs longer than 200 nt.  ncRNAs include miRNAs, piRNAs, snoRNAs, lncRNAs (eg HOTAIR).

Small ncRNAs 22 nt. In animals mediate PTGS. Control translation of mRNA into proteins.

piRNAs are ncRNAs 24-30 nt in length. They are Dicer-independent and bind PIWI subfamily of Argonatute proteins involved in maintaining stability of genome in germline cells. Transcrobed from transpoable elements and other repetitive elements. Complex formed by piRANs and PIWI proteins suppressed TE expression and mobilisation. The mechanisms include cleaving TE transcripts by IWI proteins. This is mediated through base pairing recognition by piRNA. The 2nd is heterochromatin mediated gene silencing. PIWI class protiens PIWIL1 PIWIL2 and PIWIL4 are involved in ping pong amplification cycle. This creates antisense piRNAs that can repress trasncript of origin. PIWI proteins are linked to DNA methylation.

a | MicroRNAs (miRNAs) are transcribed as individual units (primary miRNA (pri-miRNA)) or together with host genes (mirtrons). Following processing by the Drosha complex or the lariat-debranching enzyme, respectively, precursor miRNAs (pre-miRNAs) are exported from the nucleus by exportin 5 (XPO5). Further processing by Dicer and TAR RNA-binding protein 2 (TARBP2) generates mature miRNAs, which are loaded into the RNA-induced silencing complex (RISC). miRNAs function through degradation of protein-coding transcripts or translational repression. b | PIWI-interacting RNAs (piRNAs) are mainly expressed as ssRNAs from mono- or bidirectional clusters. Subsequently, additional piRNAs are produced through a PIWI-protein-catalysed amplification loop (called the 'ping-pong cycle') via sense and antisense intermediates. The PIWI ribonucleoprotein (piRNP) complex functions in transposon repression through target degradation and epigenetic silencing. c | Small nucleolar RNAs (snoRNAs) are predominantly located in introns. Following splicing, debranching and trimming, mature snoRNAs are either exported, in which case they function in ribosomal RNA (rRNA) processing, or remain in the nucleus, where they are involved in alternative splicing and additional yet unknown functions. pre-mRNA, precursor mRNA; snoRNP, small nucleolar ribonucleoprotein.

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