Mammalian introns: when the junk generates molecular diversity - PubMed
- ️Thu Jan 01 2015
Size distribution of human introns. The human genome data was downloaded from the UCSC main table browser (GRCh38, December 2013 build). Data was processed using tabular software. Analysis was performed using 277,495 introns. The lower size limit for human introns is represented by the dark arrow and is comprised between 60 and 70 bases.
Selected tracks for the human MTOR (A); NF1 (B) and MOB2 (C) genes. (A) Mechanistic target of rapamycin (serine/threonine kinase) gene (MTOR; chr1:11,166,588–11,322,608) is composed of 58 exons spanning 156,020 nucleotides. It contains 3 nested genes: MTOR-AS1 (MTOR antisense RNA 1; chr1:11,203,955–11,209,595) gene which encodes an antisense RNA across introns 24 to 27 and overlapping exon 25; ANGPTL7 (chr1:11,249,346–11,256,038) gene embedded in intron 30; RPL39P6 (chr1:11,293,020–11,293,169) gene which is a pseudogene included in intron 43; (B) Neurofibromin 1 gene (NF1; chr17:29,421,945–29,704,695) composed of 58 exons spanning 282,751 nucleotides holds 4 nested genes, 3 of which are coding genes located in intron 30 and 1 is a pseudogene (AK4P1; chr17:29,672,539–29,673,205; included in intron 42), all of which are transcribed from the opposite strand. The 3 nested genes are the oligodendrocyte myelin glycoprotein gene (OMG; chr17:29,621,668–29,624,380), ecotropic viral integration site 2A (EVI2A; chr17:29,643,428-29,648,767) and 2B (EVI2B; chr17:29,630,788–29,641,130); (C) MOB kinase activator 2 gene (MOB2; chr11:1,490,685–1,785,501) contains 13 nested genes: dual specificity phosphatase 8 (DUSP8) coding gene; KRTAP5-1/KRTAP5-2 antisense RNA 1 (KRTAP5-AS1) pseudogene; keratin associated protein 5-1 (KRTAP5-1) and 5 other paralog genes (KRTAP5-2 to -6); family with sequence similarity 99, member A (FAM99A) and member B (FAM99B) which are non-coding genes; interferon induced transmembrane protein 10 (IFITM10) and cathepsin D (CTSD) coding genes; one unannotated gene corresponding to EST GenBank AF085962. Amazingly, KRTAP5-1 gene was embedded within and oriented in the opposite direction of KRTAP5-AS1 pseudogene intron, itself oriented in the opposite direction to MOB2 intron.
Selected tracks for the human MTOR (A); NF1 (B) and MOB2 (C) genes. (A) Mechanistic target of rapamycin (serine/threonine kinase) gene (MTOR; chr1:11,166,588–11,322,608) is composed of 58 exons spanning 156,020 nucleotides. It contains 3 nested genes: MTOR-AS1 (MTOR antisense RNA 1; chr1:11,203,955–11,209,595) gene which encodes an antisense RNA across introns 24 to 27 and overlapping exon 25; ANGPTL7 (chr1:11,249,346–11,256,038) gene embedded in intron 30; RPL39P6 (chr1:11,293,020–11,293,169) gene which is a pseudogene included in intron 43; (B) Neurofibromin 1 gene (NF1; chr17:29,421,945–29,704,695) composed of 58 exons spanning 282,751 nucleotides holds 4 nested genes, 3 of which are coding genes located in intron 30 and 1 is a pseudogene (AK4P1; chr17:29,672,539–29,673,205; included in intron 42), all of which are transcribed from the opposite strand. The 3 nested genes are the oligodendrocyte myelin glycoprotein gene (OMG; chr17:29,621,668–29,624,380), ecotropic viral integration site 2A (EVI2A; chr17:29,643,428-29,648,767) and 2B (EVI2B; chr17:29,630,788–29,641,130); (C) MOB kinase activator 2 gene (MOB2; chr11:1,490,685–1,785,501) contains 13 nested genes: dual specificity phosphatase 8 (DUSP8) coding gene; KRTAP5-1/KRTAP5-2 antisense RNA 1 (KRTAP5-AS1) pseudogene; keratin associated protein 5-1 (KRTAP5-1) and 5 other paralog genes (KRTAP5-2 to -6); family with sequence similarity 99, member A (FAM99A) and member B (FAM99B) which are non-coding genes; interferon induced transmembrane protein 10 (IFITM10) and cathepsin D (CTSD) coding genes; one unannotated gene corresponding to EST GenBank AF085962. Amazingly, KRTAP5-1 gene was embedded within and oriented in the opposite direction of KRTAP5-AS1 pseudogene intron, itself oriented in the opposite direction to MOB2 intron.
Schematic representation of canonical- (A), recursive- (B), and intra- (C) splicing. Boxes and lines are exons and introns, respectively. Splicing processes are shown by dotted lines.
Different mechanisms of microRNA biogenesis. The first three panels correspond to the canonical miRNA pathway, either intergenic (miRNAs) or intronic (intronic miRNAs), and the last two panels represent new alternative pathways, either independent of the microprocessor Drosha/DGCR8 (mirtrons) or independent of DGCR8 but dependent of U1 snRNP (simtrons), both dependent on splicing to produce miRNAs. DGCR8 stands for DiGeorge syndrome critical region gene 8. Adapted from [48].
Intron distribution relative to their position in genes. About 20% of all introns subjected to alternative splicing (AS) are intron 1.
Carcino-embryonic antigen related cell adhesion molecule 6 (CAECAM6) and its novel spliced variant CAECAM6-Long (CAECAM6-L) from rat testis. Gene, mRNA and protein representation reproduced using data from [69]. Exons are numbered. Twisted arrow and star corresponded to ATG and stop codon, respectively. Intron 3 is denoted i3. Colored boxes corresponded to exons, thin line to introns except for i3, which was shown as a black box. White and grey boxes are for untranslated region (UTR) and coding sequences, respectively.
Both coding and non-coding RNAs can be produced by a given genetic locus. Intron-spliced isoforms are translated into protein while intron-retaining transcripts escape surveillance machineries and produce functional ncRNAs. Exons are numbered and represented by grey boxes and by thin lines. Arrow and star represent ATG and stop codon, respectively. In the mature transcript, the retained intron appears as a black box, UTR and coding sequences as white and grey boxes respectively.