Figure 5. Regulatory outcomes of RNA-binding proteins.

RNA-binding proteins (RBPs) regulate transcript splicing, stability, translation and localization, and many RBPs studied as splicing regulators have extended functions in the cytoplasm, affecting every subsequent step of the mRNA life cycle. a | Nuclear roles of RBPs. Step 1: RBPs control alternative splicing of precursor mRNA (pre-mRNA) to generate multiple isoforms that differ in functional activity, interactions with cofactors or post-translational modifications. Step 2: regulated intron retention targets transcript isoforms for degradation by nuclear surveillance mechanisms^200,201, or by the introduction of a premature termination codon leading to nonsense-mediated decay (NMD, shown in red; see below). Step 3: by shifting the reading frame or by including a ‘poison exon’ containing a premature translation termination codon, alternative splicing produces transcript isoforms that are degraded by NMD²⁰². Alternative splicing coupled with NMD can control the overall abundance of gene transcripts²⁰³. b | Cytoplasmic roles of RBPs. Step 4: RBPs compete with AU-binding proteins for binding at AU-rich elements in the 3′ untranslated region (UTR) to stabilize their target transcripts^110,111. Other RBPs regulate transcript stability in the cytoplasm by either competing with microRNAs for their binding sites or facilitating microRNA binding^131,204,205. RBP binding in both the 5′ UTRs and 3′ UTRs also affects translational efficiency²⁰⁶. Step 5: RBPs regulate the transport and differential localization of mRNA, which are crucial for spatial and temporal control of translation in response to activity-dependent signalling^162,207,208. The establishment of neuronal polarity and consolidation of synaptic strength through local translation of mRNAs in response to synaptic activity are some well-known examples. AAA, poly-A tail; Gppp, 5′ cap; Pol II, RNA polymerase II.