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Open Access 24-02-2024 | Psychiatry and Preclinical Psychiatric Studies - Review Article

It is not just about transcription: involvement of brain RNA splicing in substance use disorders

Authors: Luana Carvalho, Amy W. Lasek

Published in: Journal of Neural Transmission | Issue 5/2024

Abstract

Alternative splicing is a co-transcriptional process that significantly contributes to the molecular landscape of the cell. It plays a multifaceted role in shaping gene transcription, protein diversity, and functional adaptability in response to environmental cues. Recent studies demonstrate that drugs of abuse have a profound impact on alternative splicing patterns within different brain regions. Drugs like alcohol and cocaine modify the expression of genes responsible for encoding splicing factors, thereby influencing alternative splicing of crucial genes involved in neurotransmission, neurogenesis, and neuroinflammation. Notable examples of these alterations include alcohol-induced changes in splicing factors such as HSPA6 and PCBP1, as well as cocaine's impact on PTBP1 and SRSF11. Beyond the immediate effects of drug exposure, recent research has shed light on the role of alternative splicing in contributing to the risk of substance use disorders (SUDs). This is exemplified by exon skipping events in key genes like ELOVL7, which can elevate the risk of alcohol use disorder. Lastly, drugs of abuse can induce splicing alterations through epigenetic modifications. For example, cocaine exposure leads to alterations in levels of trimethylated lysine 36 of histone H3, which exhibits a robust association with alternative splicing and serves as a reliable predictor for exon exclusion. In summary, alternative splicing has emerged as a critical player in the complex interplay between drugs of abuse and the brain, offering insights into the molecular underpinnings of SUDs.

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Title: It is not just about transcription: involvement of brain RNA splicing in substance use disorders
Authors: Luana Carvalho
Amy W. Lasek
Publication date: 24-02-2024
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 5/2024
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-024-02740-y

At a glance: The STEP trials

Springer Medicine

It is not just about transcription: involvement of brain RNA splicing in substance use disorders

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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