Tudor staphylococcal nuclease: biochemistry and functions

Abstract

Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) is an evolutionarily conserved protein with invariant domain composition, represented by tandem repeat of staphylococcal nuclease domains and a tudor domain. Conservation along significant evolutionary distance, from protozoa to plants and animals, suggests important physiological functions for TSN. It is known that TSN is critically involved in virtually all pathways of gene expression, ranging from transcription to RNA silencing. Owing to its high protein-protein binding affinity coexistent with enzymatic activity, TSN can exert its biochemical function by acting as both a scaffolding molecule of large multiprotein complexes and/or as a nuclease. TSN is indispensible for normal development and stress resistance, whereas its increased expression is closely associated with various types of cancer. Thus, TSN is an attractive target for anti-cancer therapy and a potent tumor marker. Considering ever increasing interest to further understand a multitude of TSN-mediated processes and a mechanistic role of TSN in these processes, here we took an attempt to summarize and update the available information about this intriguing multifunctional protein. TSN is an evolutionarily conserved protein having a pivotal role in the regulation of gene expression. TSN acts both as a scaffolding protein and as a nuclease. TSN sustains cell viability and its cleavage by proteases facilitates cell death. TSN is implicated in key cancer-related processes and is a potent marker of various types of tumors. Open questions:How is nucleolytic activity of TSN regulated in vivo and how this affects interaction of TSN with downstream targets? What are the structural bases and functional consequences of distinct intracellular localization patterns of TSN in animals and plants? What are the molecular mechanisms of the TSN-mediated cancerogenesis?God has given you one face, and you make yourself another (William Shakespeare). Being true for all living organisms, accurate spatio-temporal regulation of gene expression is a fundamental mechanism underlying development, homeostasis and adaptation to the environment. Eukaryotic gene expression is a cumulative outcome of a multitude of molecular processes, including transcription, mRNA splicing, stability and translation, chromatin modification, as well as protein stability and modification. Each of these processes is in turn controlled by a highly dedicated repertoire of proteins. However, one protein, Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) appears to act in most of the gene expression pathways.TSN is an evolutionarily conserved protein found in all eukaryotic lineages, except budding yeast, Saccharomyces cerevisiae. Conservation along significant evolutionary distance suggests important physiological functions for TSN. Invariant domain composition of TSN comprises tandem repeat of four staphylococcal nuclease (SN)-like domains (hereafter referred to as SN domains) at the N terminus and a fusio...

Polysomes, Stress Granules, and Processing Bodies: A Dynamic Triumvirate Controlling Cytoplasmic mRNA Fate and Function

“…TSNs are evolutionarily conserved cytoskeletonassociated RBPs characterized by four complete N-terminal staphylococcal nuclease domains followed by a central Tudor domain and a partial SN domain at the C terminus (Gutierrez-Beltran et al, 2016). A plant TSN was first described in rice as an RBP required for the transport of a subgroup of seed storage RNAs to a subdomain of the endosperm endoplasmic reticulum (Tian and Okita, 2014).…”

Global Tudor‐SN transgenic mice are protected from obesity‐induced hepatic steatosis and insulin resistance

“…Tudor-staphylococcal nuclease (SN), also known as staphylococcal nuclease domain containing 1 (Snd1), is a highly conserved and ubiquitously expressed multifunctional protein (15)(16)(17)(18)(19)(20)(21)(22)(23). This enzyme comprises a tandem repeat of 4 SN-like domains (referred to as SN domains) at the N terminus and a fusion of a Tudor domain with a partial SN domain at the C terminus (referred to as a TSN domain) (22). Tudor-SN is normally localized in the cytoplasm except under certain circumstances, such as stress, in which it may shuttle between the nucleus and the cytoplasm (16,19,23).…”

“…Tudor-SN, which is indispensable for normal development, promotes cell-cycle progression by facilitating E2F-1-mediated gene transcription (17). Owing to a high protein-protein binding affinity coexisting with enzymatic activity, Tudor-SN can exert its biochemical function by acting as a scaffolding molecule for large multiprotein complexes, as a nuclease, or both (22). In terms of the function of Tudor-SN in lipid metabolism, it has been found in the cytosolic lipid droplets of lactating mammary glands of cows and mice (24) and acts as a factor to promote lipoprotein phospholipid localization in lipid droplets in rat hepatocytes (25,26).…”

Multifunctional RNA Binding Protein OsTudor-SN in Storage Protein mRNA Transport and Localization

“…The multifunctional properties of Tudor-SN can be attributed to its complex structure, consisting of multiple domains within the 4SN and Tsn modules (Gutierrez-Beltran et al, 2016). As a key component in RNA splicing, processing, and editing, the 4SN module has RNA-binding and RNA cleavage activities (Caudy et al, 2003;Scadden, 2005;Li et al, 2008).…”