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Minor spliceosome


The minor spliceosome is a ribonucleoprotein complex that catalyses the removal (splicing) of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs in plant, insects, vertebrates and some fungi (Rhizopus oryzae). This process is called noncanonical splicing, as opposed to U2-dependent canonical splicing. U12-type introns represent less than 1% of all introns in human cells. However they are found in genes performing essential cellular functions.

A notable feature of eukaryotic nuclear pre mRNA introns is the relatively high level of conservation of the primary sequences of 5’ and 3’ splice sites over a great range of organisms.

Since 1989 till 1991, several groups reported four independent examples of introns with a splice site that differed from the common intron:

In 1991 by comparing the intron sequences of P120 and CMP genes, IJ Jackson reported the existence of ATATCC (5') and YYCAC (3') splice sites in these introns. The finding indicated a possible novel splicing mechanism.

In 1994, S.L. Hall and R.A Padgett compared the primary sequence of all reports on the four genes mentioned above. The results suggested a new type of introns with ATATCCTT 5’ splice site and YCCAC 3’ splice site and an almost invariant TCCTTAAC near the 3’ end of the introns (so called 3’ upstream element). A search for small nuclear RNA sequences that are complementary to these splice sites, suggested U12 snRNA (matches 3’ sequence) and U11 snRNA (matches 5’sequence) as being putative factors involved in splicing of this new type of introns.

In all these four genes, the pre-mRNA contains other introns whose sequences conform to those of major class introns. Neither the size nor the position of the AT–AC intron within the host gene is conserved.

In 1996, Woan-Yuh Tarn and Joan A. Steitz described an in vitro system that splices a pre-mRNA substrate containing an AT–AC intron derived from the human P120 gene. Psoralen cross-linking confirms the base-pairing interaction predicted by Hall and Padgett between the branch site of the pre-mRNA substrate and U12 RNA. Native gel electrophoresis reveals that U11, U12, and U5 snRNPs assemble onto the P120 pre-mRNA to form splicing complexes.

Although originally referred to as AT-AC introns, not all these introns are delimited by AT-AC dinucleotides. Some of them have GT-AG or AT-AG ends, at least. Thus, it is more correct to speak about the splicing machinery which is used to process them, differentiating between U2-type (canonical or major) and U12-type (non-canonical or minor). The main determinants for distinguishing U2- and U12-type introns are 5’ splice site and branch site sequences.


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