The significant other: splicing by the minor spliceosome

Abstract

The removal of non-coding sequences, introns, from the mRNA precursors is an essential step in eukaryotic gene expression. U12-type introns are a minor subgroup of introns, distinct from the major or U2-type introns. U12-type introns are present in most eukaryotes but only account for less than 0.5% of all introns in any given genome. They are processed by a specific U12-dependent spliceosome, which is similar to, but distinct from, the major spliceosome. U12-type introns are spliced somewhat less efficiently than the major introns, and it is believed that this limits the expression of the genes containing such introns. Recent findings on the role of U12-dependent splicing in development and human disease have shown that it can also affect multiple cellular processes not directly related to the functions of the host genes of U12-type introns. At the same time, advances in understanding the regulation and phylogenetic distribution of the minor spliceosome are starting to shed light on how the U12-type introns and the minor spliceosome may have evolved. © 2012 John Wiley & Sons, Ltd.

Extending the critical regions for mutations in the non‐coding gene RNU4ATAC in another patient with Roifman Syndrome

“…There are discrepant results for NR_023343.1:n.116A which, depending on the publication, either had or had not been judged as part of the Sm protein‐binding site. The core region, essential for splicing, is so far defined from NR_023343.1:n.117 to NR_023343.1:n.124 2, 3, 13. Regarding the clinical data obtained in the study presented here, NR_023343.1:n.116 also belongs to the critical region important for splicing, which has to be confirmed in further functional studies (Figure 1).…”

“…Both subregions are separated by the 5′stem‐loop, which functions as a binding platform for proteins required for tri‐snRNP formation of U4atac, U6atac, and U5. The 3′stem‐loop immediately precedes a binding site for Sm proteins, which are important for snRNP assembly and import into the nucleus2, 3, 12 (Figure 1). …”

“…RNU4ATAC codes for the small nuclear RNA (snRNA) U4atac, which is part of the minor spliceosome complex that catalyzes the splicing of an atypical class of introns (U12‐ or “ATAC”‐type) from eukaryotic pre‐mRNA. Approximately 800 human genes contain U12‐type introns 3. Pathogenic variants in RNU4ATAC are associated with the recessive disorder microcephalic osteodysplastic primordial dwarfism, type 1 (MOPD1, OMIM #210710) and the less severe Roifman Syndrome.…”

Minor class splicing shapes the zebrafish transcriptome during development

“…Minor class introns are excised by U12-type spliceosomes, which are analogous in function and similar in composition to U2-type spliceosomes; each comprise five small nuclear RNAs (snRNAs) and hundreds of associated proteins (6). Although the U5 snRNA is shared between the two complexes, the U12-type spliceosome contains four unique snRNAs (U11, U12, U4atac, and U6atac) (7)(8)(9) and at least seven unique proteins (10). Since its discovery two decades ago, the existence of this highly conserved, second splicing pathway has been an intriguing aspect of gene expression.…”

L’épissage des ARN pré-messagers : quand le splicéosome perd pied

“…Plusieurs types d'épissage alternatif ont été caracté-risés, dont l'événement majoritaire est l'exclusion d'un permettant un remodelage des complexes indispensable à la réaction d'épissage [3,50] (➜). Il est important de mentionner que le splicéosome existe sous deux formes partiellement superposables, le splicéosome « majeur » (voir plus haut), dont dépend la majorité des introns, et le splicéosome « mineur » qui prend en charge moins de 1 % des introns humains et utilise les snRNP U11, U12, U4atac, U5 et U6atac [4]. Les introns reconnus par le splicéosome mineur présentent des sites AT (site 5') et AC (site 3'), ou des sites consensus reconnus par le splicéosome majeur, GT (en 5') et AG (en 3').…”