![]() TIA1 interacts with the splicing machinery facilitating alternative splicing site recognition. However, while efforts have been made to understand TIA1 function in the stress response supporting cell survival, it is becoming clear that TIA1 also contributes to cellular physiology in homeostatic states. TIA1 is an RBP that recruits RNAs into stress granules as part of the adaptive response to stress. ![]() For example, mutations in multiple RBP genes have been shown to increase the risk for ASD. Importantly, abnormal post-transcriptional regulation associates with neurological diseases and is consistently implicated in neurodevelopmental disorders including autism spectrum disorder (ASD). Post-transcriptional regulation mechanisms play pivotal roles during neurodevelopment and in neuronal function. RBPs play a central role in post-transcriptional regulation through their association with mRNAs in all stages of mRNA metabolism, from mRNA biogenesis in the nucleus to sub-cellular localization and degradation in the cytoplasm. RNA-binding proteins (RBPs) are modular regulatory proteins containing one or more domains for specific contact with RNAs. They modify the proteome allowing for the manifestation of distinct physiological properties in a cell-specific manner, independent of transcriptional regulation. Post-transcriptional mechanisms contribute to the differential gene expression profile of cells containing the same genetic blueprint. Post-transcriptional regulation is the collection of mechanisms regulating gene expression that start operating co-transcriptionally through the processing of the pre-mRNAs, and play critical roles in cellular homeostasis and development. ![]() Our results reveal TIA1 mRNA targets in hESCs and during human neurodevelopment, indicate that translation repression is a key process targeted by TIA1 binding and implicate TIA1 function in neuronal differentiation. Additionally, we found that most TIA1 mRNA targets have reduced ribosomal engagement levels. The vast majority of mRNA targets in hESC were genes associated with neurodevelopment and included autism spectrum disorder-risk genes that were not bound in neurons. We identified 2400, 845, and 330 TIA1 mRNA targets in hESCs, NPC, and neurons, respectively. While there was no change in TIA1 protein levels, the number of TIA1 targeted mRNAs decreased from pluripotent cells to neurons. To identify the mRNAs targeted by TIA1 during the first stages of human neurodevelopment, we performed RNA immunoprecipitation-sequencing (RIP-seq) on human embryonic stem cells (hESCs) and derived neural progenitor cells (NPCs), and cortical neurons under unstressed conditions. However, the identity of mRNAs regulated by TIA1 during neurodevelopment under unstressed conditions is still unknown. TIA1 is an RNA-binding protein that can regulate splicing, stability, or translation of target mRNAs, and has been shown to play critical roles in stress response and neurodevelopment. While transcriptional pathways regulating neurodevelopment are well characterized, post-transcriptional programs are still poorly understood. Neuronal development is a tightly controlled process involving multi-layered regulatory mechanisms.
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