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Fig. 1 | Genome Biology

Fig. 1

From: Splicing heterogeneity: separating signal from noise

Fig. 1

Stochastic events in splicing. The spliceosome is a single-turnover enzyme that assembles and disassembles for each splicing event. Splicing consists of a complex sequence of steps, and each step represents several biochemical reactions. These reactions involve binding and dissociation events, which include random variables at the molecular level. a Schematic representation of the steps associated with mRNA production: transition of the promoter between a repressed and an active state, transcription, co-transcriptional or post-transcriptional splicing to create heterogenous isoforms and mRNA degradation. b Kinetic scheme for co-transcriptional spliceosome assembly. The formation of the catalytically competent spliceosome starts with splice site recognition, which is a highly dynamic process. Although the in vivo measurements of snRNP kinetics are still missing, in vitro experiments provide evidence for the reversible binding of almost all of the major subcomplexes to the nascent RNA (e.g., the pairing between U1 and 5′ss, U2 and branchpoint, the binding of tri-snRNP and NTC are in a kinetic range of k = 0.13–0.35 min− 1). The binding dynamics between the U2AF complex and poly-pyrimidine tract and 3′ss are still poorly understood. The binding of heterogeneous nuclear ribonucleoproteins (hnRNPs) and SR proteins also regulates splicing dynamics. Their kinetics need to be further explored. c Variability of splice sites in the human genome. (i) Consensus motifs of the U2-type 3′ splice sites with AG at the border. (ii) Non-canonical motifs of U2-type 3′ splice sites with dinucleotides other than AG at the border. (iii) Consensus motifs of the U1-type 5′ splice sites with GT at the border. (iv) Non-canonical motifs of U1-type 5′ splice sites with dinucleotides other than GT at the border. NTC NineTeen complex, Pol II RNA polymerase II, snRNP small nuclear ribonucleoprotein

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