SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape

Abstract In eukaryotes, DNA is packaged into chromatin, which presents significant barriers to transcription. Non-histone chromatin proteins such as the Heterochromatin Protein 1 (HP1) proteins are critical regulators of transcription, contributing to gene regulation through a variety of molecular mechanisms. HP1 proteins are highly conserved, and many eukaryotic genomes contain multiple HP1 genes. Given the presence of multiple HP1 family members within a genome, HP1 proteins can have unique as well as shared functions. Here, we review the mechanisms by which HP1 proteins contribute to the regulation of transcription. Focusing on the Drosophila melanogaster HP1 proteins, we examine the role of these proteins in regulating the transcription of genes, transposable elements, and piRNA clusters. In D. melanogaster , as in other species, HP1 proteins can act as transcriptional repressors and activators. The available data reveal that the precise impact of HP1 proteins on gene expression is highly context dependent, on the specific HP1 protein involved, on its protein partners present, and on the specific chromatin context the interaction occurs in. As a group, HP1 proteins utilize a variety of mechanisms to contribute to transcriptional regulation, including both transcriptional (i.e. chromatin-based) and post-transcriptional (i.e. RNA-based) processes. Despite extensive studies of this important protein family, open questions regarding their functions in gene regulation remain, specifically regarding the role of hetero- versus homodimerization and post-translational modifications of HP1 proteins. 

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Functions of HP1 proteins in transcriptional regulation

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ABSTRACT Initially discovered by genetic screens in budding yeast, SPT5 and its partner SPT4 form a stable complex known as DSIF in metazoa, which plays pleiotropic roles in multiple steps of transcription. SPT5 is the most conserved transcription elongation factor, being found in all three domains of life; however, its structure has evolved to include new domains and associated posttranslational modifications. These gained features have expanded transcriptional functions of SPT5, likely to meet the demand for increasingly complex regulation of transcription in higher organisms. This review discusses the pleiotropic roles of SPT5 in transcription, including RNA polymerase II (Pol II) stabilization, enhancer activation, Pol II pausing and its release, elongation, and termination, with a focus on the most recent progress of SPT5 functions in regulating metazoan transcription.

https://www.tandfonline.com/doi/pdf/10.1080/21541264.2022.2103366?needAccess=true

The pleiotropic roles of SPT5 in transcription

ARS2/SRRT is an essential eukaryotic protein that has emerged as a critical factor in the sorting of functional from non-functional RNA polymerase II (Pol II) transcripts. Through its interaction with the Cap Binding Complex (CBC), it associates with the cap of newly made RNAs and acts as a hub for competitive exchanges of protein factors that ultimately determine the fate of the associated RNA. The central position of the protein within the nuclear gene expression machinery likely explains why its depletion causes a broad range of phenotypes, yet an exact function of the protein remains elusive. Here, we consider the literature on ARS2/SRRT with the attempt to garner the threads into a unifying working model for ARS2/SRRT function at the nexus of Pol II transcription, transcript maturation and quality control.

Roberta Dollinger

Papers

Regulation of Promoter Proximal Pausing of RNA Polymerase II in Metazoans.