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U12splicing wiki (internal)

Viikki Biocenter

Institute of Biotechnology

University of Helsinki


The key focus of our lab is pre-mRNA splicing and it's regulation. Additionally we investigate genomics, tanscriptomics and pre-mRNA processing with various non-model organisms.

Our studies of pre-mRNA splicing are centered on the U12-dependent spliceosome so called "minor spliceosome") which is thought regulate gene expression mostly by adjusting the cellular level of individual mRNAs rather than controlling the mRNA information content by alternative splicing. The targets of this splicing machinery are a class of rare introns, called U12-type introns. These introns have recognition sequences that are longer and much more conserved than the ones from the standard U2-type introns. These sequences are removed by a separate U12-dependent spliceosome, while the majority of introns are excised by U2-dependent spliceosome. In humans there are approximately 600 U12-type introns belonging mostly to so called "information processing" gene group, which is linked to important cellular functions as transcription, translation, DNA replication/repair, and certain signaling pathways.

The key question in the field relate to the biological significance of having two separate spliceosomes in the cells of higher eukaryotes. The U12-type introns are only rarely involved in alternative splicing as compared to the standard U2-type introns. Rather it seems that the role of the U12-dependent spliceosome is to regulate gene expression by adjusting the rate of intron excision as these introns are spliced more slowly or less efficiently compared to the normal U2-type introns. Currently two human diseases MOPD1/TALS and IGHD1 have been reported to arise through mutations in either snRNA or protein components of the minor spliceosome.

Our research is focused on the regulatory aspects of the U12-type spliceosome and the molecular mechanisms of human diseases with defects in the minor spliceosome components. Additionally, we are also studying mechanism of assembly and the architecture of this spliceosome.

A model for feedback regulation of the U12-dependent spliceosome proteins. From Verbeeren et al. (2010), Mol Cell 37, 821-833

Our studies on the genomics of non-model organism are mainly concentrated on the Glanville fritillary butterfly (Melitae cinxia) together with Metapopulation Research Group headed by prof. Ilkka Hanski. Melitae cinxia is considered to one of the key ecological model systems in metapopulation biology. In particularly, the Åland metapopulation has been a subject of extensive ecological research and mathematical modeling.

The key aims in this research have been to develop genomics tools to uncover genomic variation that affects population structure, in particular, variation on dispersal rate and other life history traits within the Åland metapopulation. In order to fulfill these goals we have earlier determined the transcriptome and more recently
the whole genome sequence
of the Glanville Fritillary.