Temporal patterning of the vertebrate developing neural tube

Sagner, Andreas

doi:10.1016/j.gde.2024.102179

Cited by 1 publication

(1 citation statement)

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“…During cell specification, both transcriptional and post-transcriptional mechanisms combine to gradually refine patterns of protein production and promote the formation of specific cell types. From the initial delineation of the mammalian trophectoderm and inner cell mass lineages by mutually exclusive networks of transcription factors [1][2][3][4][5][6] to the production of specific neuronal subtypes within the developing neural tube [7,8], developmentally regulated transcriptional control of gene expression is widespread and critically important for determining cell identity. In addition to transcription, post-transcriptional mechanisms of gene expression control also contribute to organismal development and cell specification [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The polyadenosine RNA binding protein Nab2 regulates alternative splicing and intron retention duringDrosophila melanogasterbrain development

Kelly,

Paschack,

Mishra

et al. 2024

Preprint

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The regulation of cell-specific gene expression patterns during development requires the coordinated actions of hundreds of proteins, including transcription factors, processing enzymes, and many RNA binding proteins (RBPs). RBPs often become associated with a nascent transcript immediately after its production and are uniquely positioned to coordinate concurrent processing and quality control steps. Since RNA binding proteins can regulate multiple post-transcriptional processing steps for many mRNA transcripts, mutations within RBP-encoding genes often lead to pleiotropic effects that alter the physiology of multiple cell types. Thus, identifying the mRNA processing steps where an RBP functions and the effects of RBP loss on gene expression patterns can provide a better understanding of both tissue physiology and mechanisms of disease. In the current study, we have investigated the coordination of mRNA splicing and polyadenylation facilitated by the Drosophila RNA binding protein Nab2, an evolutionary conserved ortholog of human ZC3H14. ZC3H14 loss in human patients has previously been linked to alterations in nervous system function and disease. Both fly Nab2 and vertebrate ZC3H14 bind to polyadenosine RNA and have been implicated in the control of poly(A) tail length. Interestingly, we show that fly Nab2 functionally interacts with components of the spliceosome, suggesting that this family of RNA biding proteins may also regulate alternative splicing of mRNA transcripts. Using RNA-sequencing approaches, we show that Nab2 loss causes widespread changes in alternative splicing and intron retention. These changes in splicing cause alterations in the abundance of protein isoforms encoded by the affected transcripts and may contribute to phenotypes, such as decreases in viability and alterations in brain morphology, observed in Nab2 null flies. Overall, these studies highlight the importance of RNA binding proteins in the coordination of post-transcriptional gene expression regulation and potentially identify a class of proteins that can coordinate multiple processing events for specific mRNA transcripts.

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