Biology subjects

Latifkar, A.

Publications and source records attributed to Latifkar, A..

3 recordsLinked to original sources

bioRxiv2025

mRNA poly(A)-tail length is a battleground for coronavirus-host competition

Most eukaryotic mRNAs contain a poly(A) tail, which in post-embryonic cells enhances their stability. Many cytoplasmic RNA viruses also harbor poly(A) tails on their genomic RNA and mRNAs. Here, we report that coronavirus infection causes cytoplasmic poly(A)-binding protein (PABPC) activity to become limiting, which preferentially destabilizes short-tailed host mRNAs, occurring before the action of virally encoded mRNA-decay factor nsp1. In this environment hostile to poly(A) tails, viral RNAs maintain a narrow tail-length distribution centering on 70-80 nucleotides across infection cycles. They do this through two mechanisms. First, viral tails are extended during RNA synthesis within double-membrane vesicles; second, viral tails are capped by a complex that includes PABPC1 and CSDE1 and slows tail shortening. Our findings suggest poly(A)-tail length is an arena of host- virus conflict, in which preserving tail lengths of viral mRNAs promotes their cytoplasmic dominance. HighlightsO_LIPABPC1 becomes limiting during coronavirus infection C_LIO_LILimiting PABPC1 promotes decay of short-tailed host mRNAs--independently of nsp1 C_LIO_LIThe tail lengths of coronaviral mRNAs are extended during their synthesis in DMVs C_LIO_LIViral tails are capped by PABPC1 and CSDE1, which protects against deadenylation C_LI

molecular biology↗

bioRxiv2025

Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells

In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique aspects of mitosis require substantial adaptations to the core gene expression programs. Indeed, during interphase, the homeostatic control of mRNA levels involves a constant balance of transcription and degradation, with a median mRNA half-life of [~]2-4 hours. If such short mRNA half-lives persisted in mitosis, cells would be expected to quickly deplete their transcriptome in the absence of new transcription. Here, we report that the transcriptome is globally stabilized during prolonged mitotic delays. Typical mRNA half-lives are increased >4-fold in mitosis compared to interphase, thereby buffering mRNA levels in the absence of new synthesis. Moreover, the poly(A)-tail-length profile of mRNAs changes in mitosis, strongly suggesting a mitotic repression of deadenylation. We further show that mRNA stabilization in mitosis is dependent on cytoplasmic poly(A)-binding proteins PABPC1&4. Depletion of PABPC1&4 disrupts the maintenance of mitotic arrest, highlighting the critical physiological role of mitotic transcriptome buffering. HighlightsO_LIThe cellular transcriptome is globally stabilized during prolonged mitotic arrest C_LIO_LIDistinct poly(A)-tail-length profile of mRNAs in mitosis suggests repression of deadenylation C_LIO_LImRNA stabilization in mitosis is dependent on PABPC1 and PABPC4 C_LIO_LIDegradation of mRNAs during mitosis compromises maintenance of mitotic arrest C_LI

cell biology↗

bioRxiv2021

IGF2BP2 Promotes Cancer Progression by Degrading the RNA Transcript Encoding a v-ATPase Subunit

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds to various RNA transcripts and promotes cancer progression, although little is known regarding its regulation. Here we show IGF2BP2 is a substrate of the deacetylase and tumor suppressor sirtuin 1 (SIRT1) and regulates the expression of the vacuolar ATPase subunit ATP6V1A. SIRT1 down-regulation in aggressive cancers leads to increased acetylation of IGF2BP2 which recruits the XRN2 nuclease to degrade the ATP6V1A transcript, decreasing its expression. This impairs lysosomal function and results in the production of a secretome that enhances cancer cell proliferation and metastasis. These findings describe a previously unrecognized role for IGF2BP2 in the degradation of an mRNA transcript essential for lysosomal function and highlight how its sirtuin-regulated acetylation state can have significant biological and disease consequences. One Sentence SummaryAcetylation of the RNA binding protein IGF2BP2, upon down-regulation of SIRT1, leads to degradation of the transcript encoding ATP6V1A and impaired lysosomal function in aggressive cancer cells.

cell biology↗