A day in the life of the spliceosome

Abstract

One of the most amazing findings in molecular biology was the discovery that eukaryotic genes are discontinuous, interrupted by stretches of non-coding sequence. The subsequent realization that the intervening regions are removed from pre-mRNA transcripts via the activity of a common set of small nuclear RNAs (snRNAs), which assemble together with associated proteins into a spliceosome, was equally surprising. How do cells orchestrate the assembly of this molecular machine? And how does the spliceosome accurately recognize exons and introns to carry out the splicing reaction? Insights into these questions have been gained by studying the life cycle of spliceosomal snRNAs from their transcription, nuclear export and reimport, all the way through to their dynamic assembly into the spliceosome. This assembly process can also affect the regulation of alternative splicing and has implications for human disease.

Graded requirement for the spliceosome in cell cycle progression

“…38 In addition, spliceosome assembly and maturation occurs at the Cajal bodies, nuclear bodies whose size and number change during the different phases of the cell cycle and are disassembled during mitosis. 39,40 Thus reduced spliceosome activity during mitosis due to inhibition and reduced assembly/maturation might explain a requirement for higher spliceosome dosage at this stage. Higher spliceosome levels during mitosis might compensate for the repression and maintain appropriate levels of splicing of genes transcribed and translated in mitosis, such as cyclin B1.…”

Proper splicing contributes to visual function in the aging Drosophila eye

“…Alternative splicing, the differential use of exons to produce distinct transcripts occurs at over 90% and 60% of protein‐coding genes in humans and Drosophila respectively (Graveley et al, 2011; Wang et al, 2008). The binding of splicing factors to elements within the nascent transcript largely governs the differential inclusion of exons, thereby determining the splicing outcome of a particular transcript (Matera & Wang, 2014). Knockdown of individual splicing factors in cultured Drosophila cells revealed that half of all splicing events are regulated by more than one splicing factor, illustrating the complicated and combinatorial effect of splicing factors in determining splice‐site usage (Brooks et al, 2015).…”

SMN - A chaperone for nuclear RNP social occasions?

“…20 While the genetic etiology of the disease is well-established, the molecular role of SMN in the disease is largely unknown and is the topic of many reviews. [25][26][27][28][29][30][31][32][33][34] …”

“…[34][35][36][37] The Sm-class snRNPs consist of uridine-rich snRNAs (e.g. U1, U2, U4, U5), several specific proteins that are unique to each snRNA, and a set of 7 common Sm proteins (B/ B', D1, D2, D3, E, F, and G).…”