https://www.normalesup.org/~vorgogoz/articles/D.pachea-references/alternative-splicing/Stamm2005-alternative-splicing-review.pdf

Function of alternative splicing.

http://sites.utoronto.ca/intron/blencowecell2006.pdf

Alternative Splicing: New Insights from Global Analyses

https://www.cell.com/cell/pdf/S0092-8674(11)00949-4.pdf

An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming

Specificity is key to biological regulation. Two families of RNA binding proteins, heterogeneous nuclear ribonucleoproteins and serine-arginine-rich proteins, were initially thought to have redundant or nonspecific biochemical functions. Recently, members of these families have been found as components of distinct regulatory complexes with highly specific and essential roles in mRNA metabolism. Here we discuss the basis for their functional specificity and the mechanisms of action of some of their characteristic protein domains.

Building specificity with nonspecific RNA-binding proteins.

Comprehensive proteomics analyses of spliceosomal complexes are currently limited to those in humans, and thus, it is unclear to what extent the spliceosome's highly complex composition and compositional dynamics are conserved among metazoans. Here we affinity purified Drosophila melanogaster spliceosomal B and C complexes formed in Kc cell nuclear extract. Mass spectrometry revealed that their composition is highly similar to that of human B and C complexes. Nonetheless, a number of Drosophila-specific proteins were identified, suggesting that there may be novel factors contributing specifically to splicing in flies. Protein recruitment and release events during the B-to-C transition were also very similar in both organisms. Electron microscopy of Drosophila B complexes revealed a high degree of structural similarity with human B complexes, indicating that higher-order interactions are also largely conserved. A comparison of Drosophila spliceosomes formed on a short versus long intron revealed only small differences in protein composition but, nonetheless, clear structural differences under the electron microscope. Finally, the characterization of affinity-purified Drosophila mRNPs indicated that exon junction complex proteins are recruited in a splicing-dependent manner during C complex formation. These studies provide insights into the evolutionarily conserved composition and structure of the metazoan spliceosome, as well as its compositional dynamics during catalytic activation.

Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes.

Posttranscriptional regulation is of fundamental importance for establishing the gene expression programs that determine sexual identity in the fruitfly Drosophila melanogaster. The protein Sex-lethal acts as a master regulatory switch, being expressed exclusively in female flies and inducing female-specific patterns of alternative splicing on target genes. As a consequence, other regulatory factors are expressed in a sex-specific manner, and these factors control somatic and germline sexual differentiation, sexual behavior and X chromosome dosage compensation. Here, we review the molecular mechanisms responsible for splicing regulation in Drosophila sexual determination.

J Valcárcel

Papers

Splicing regulation in Drosophila sex determination.