Evolution of alternative RNA-splicing

Abstract

Pojava alternativnog prekrajanja nesumnjivo predstavlja iznimno važan korak u evoluciji eukariota. Iako nije poznato kada se točno pojavilo, zasigurno je od tada snažno povećalo kodirajući potencijal genoma. Ono je nastalo kao svojevrsna nadogradnja na prekrajanje pre-mRNA. Prekrajanje RNA nastalo je kao posljedica pojave introna u ranim genomima koji su se morali izrezivati iz transkripata. Introni najvjerojatnije vuku transpozonsko porijeklo što im je omogućilo brzo širenje drevnim genomima. Kompleksnost sustava za prekrajanje samo se povećavala tijekom evolucije, ali osnovni mehanizam ostao je isti. Otprilike u vrijeme odvajanja eukariota od arheja, u ranom pretku eukariotske skupine pojavili su se snRNA i Sm proteini koji su asocirali u ribonukleoproteine (snRNP) koji su katalizirati prekrajanje te je time značajno smanjen selektivni pritisak na intronske sljedove jer mogućnost izrezivanja više nije ovisila o vlastitoj sekundarnoj strukturi. Uz to, snRNP-i su mogli uspostaviti interakciju s novonastalim skupinama proteina – SR i hnRNP koji su ih regulirali. To predstavlja začetak spliceosoma i alternativnog prekrajanja, a obje karakteristike su bile već prisutne kod najkasnijeg zajedničkog pretka eukariota. Od tada, središnje jedinice spliceosoma su do danas ostale jako dobro očuvane među svim proučenim eukariotima, ali je regulacija alternativnog prekrajanja divergirala i izravno utjecala na građu i način života eukariotskih organizama.Appearance of alternative splicing undoubtedly marks a crucial step in eukaryotic evolution. Even though it's not clear when exactly this phenomenon appeared, it must have strongly increased the coding potential of genomes. It clearly appeared as an upgrade to pre-mRNA splicing. RNA splicing came about as a consequence of introns existing in early genomes, which should have been cut out from transcripts. Introns probably derived from transposons, which initially gave them the ability to spread across ancient genomes quickly. The complexity of the splicing system increased through the process of evolution, but the main mechanism remained the same. Approximately at the time of eukaryotic divergence from archaea, in early ancestor of eukaryotic group, snRNA and Sm proteins appeared that associated into ribonucleoproteins (snRNP) and could catalyse RNA splicing. This strongly relaxed the selection pressure on intronic sequences because their ability to be spliced out didn’t depend on their secondary structure anymore. Also, snRNPs were able to interact with newly arisen protein groups – SR and hnRNP which regulated them. This marks the beginning of spliceosome and alternative splicing and both characteristics were already present in the last eukaryotic common ancestor. Since that time, core spliceosomal subunits remained highly conserved between all studied eukaryotes, but alternative splicing regulation diverged and directly influenced the structure and lifestyle of eukaryotic organisms in general