Question

Is the spliceosome a cis- or trans-acting factor and why?

Answer 1

The sequential phosphodiester transfer reactions involved in splicing are catalyzed by large ribonucleoprotein complexes known as spliceosomes. Containing more than 100 core proteins and five small nuclear RNAs (snRNAs U1, U2, U4, U5, and U6), spliceosomes may be the most complex machines in the cell.

The components of Spliceosome are trans-acting factors while the sequences involved in their recognition are cis-acting in nature.

Because

CORE SPLICING SIGNALS
Three sites, the 5′ splice site (5′ss), the 3′ splice site (3′ss), and the branch point sequence (BPS), participate in the splicing reaction and are present in every intron, and thus are known as the core splicing signals. These signals are recognized multiple times during spliceosome assembly, with the 5′ss interacting initially with U1 and later with U6 snRNP, and the BPS interacting with SF1/mBBP and later with U2 snRNP. A typical human gene contains relatively short exons (typically, 50–250 base pairs [bp] in length) separated by much larger introns (typically, hundreds to thousands of base pairs or more) that on average account for >90% of the primary transcript. This transcript geometry, and the predominant exon-skipping phenotype of splice site mutations, are consistent with the idea that in mammals splice sites are predominantly recognized in pairs across the exon through “exon definition”. Exon definition involves initial interaction across the exon between factors recognizing the 5′ss and the upstream 3′ss, whereas in the alternative model, intron definition, interactions occur first across the intron between factors recognizing the 5′ss and the downstream 3′ss.
Large part from the presence of numerous cis-regulatory elements that serve as either splicing enhancers or silencers. These elements are conventionally classified as exonic splicing enhancers (ESEs) or silencers (ESSs) if from an exonic location they function to promote or inhibit inclusion of the exon they reside in, and as intronic splicing enhancers (ISEs) or silencers (ISSs) if they enhance or inhibit usage of adjacent splice sites or exons from an intronic location. In general, these splicing regulatory elements (SREs) function by recruiting trans-acting splicing factors that activate or suppress splice site recognition or spliceosome assembly by various mechanisms. Alternative splicing is regulated by cis-acting elements within pre-mRNAs and trans-acting factors. The essential cis-acting elements are the 5′ splice site, the 3′ splice site, as well as the branchpoint sequence, which conform to partially conserved motifs that are recognized by cognate trans-acting factors. Additional cis-acting elements that regulate alternative splicing include exonic or intronic splicing enhancers and silencers (ESEs, ISEs, ESSs, ISSs), which respectively activate or repress use of particular splice sites or exon inclusion. Trans-acting factors regulate alternative splicing by associating with cis-acting elements, and include serine/arginine (SR)-rich proteins as well as heterogeneous nuclear ribonucleoproteins (hnRNPs). So, The spliceosome refers to a complex of nuclear RNA-binding proteins, which processes pre-mRNA into spliced mature mRNA. Among the subunits of the spliceosome are a group of 30 structurally related proteins known as heterogeneous nuclear ribonuclear proteins, which are called hnRNP.