Cytoplasmic regulation of the poly(A) tail length as a potential therapeutic target

Abstract

Virtually all mRNAs acquire a poly(A) tail cotranscriptionally, but its length is dynamically regulated in the cytoplasm in a transcript-specific manner. The length of the poly(A) tail plays a crucial role in determining mRNA translation, stability, and localization. This dynamic regulation of poly(A) tail length is widely used to create posttranscriptional gene expression programs, allowing for precise temporal and spatial control. Dysregulation of poly(A) tail length has been linked to various diseases, including cancers, inflammatory and cardiovascular disorders, and neurological syndromes. Cytoplasmic poly(A) tail length is maintained by a dynamic equilibrium between cis-acting elements and cognate factors that promote deadenylation or polyadenylation, enabling rapid gene expression reprogramming in response to internal and external cellular cues. While cytoplasmic deadenylation and its pathophysiological implications have been extensively studied, cytoplasmic polyadenylation and its therapeutic potential remain less explored. This review discusses the distribution, regulation, and mechanisms of cytoplasmic polyadenylation element-binding proteins(CPEBs), highlighting their dual roles in either promoting or repressing gene expression depending on cellular context. We also explore their involvement in diseases such as tumor progression and metastasis, along with their potential as targets for novel therapeutic strategies.