A jack of all trades: the RNA‐binding protein vigilin

Abstract

The vigilin family of proteins is evolutionarily conserved from yeast to humans and characterized by the proteins' 14 or 15 hnRNP K homology (KH) domains, typically associated with RNA-binding. Vigilin is the largest RNA-binding protein (RBP) in the KH domain-containing family and one of the largest RBP known to date. Since its identification 30 years ago, vigilin has been shown to bind over 700 mRNAs and has been associated with cancer progression and cardiovascular disease. We provide a brief historic overview of vigilin research and outline the proteins' different functions, focusing on maintenance of genome ploidy, heterochromatin formation, RNA export, as well as regulation of translation, mRNA transport, and mRNA stability. The multitude of associated functions is reflected by the large number of identified interaction partners, ranging from tRNAs, mRNAs, ribosomes and ribosome-associated proteins, to histone methyltransferases and DNA-dependent protein kinases. Most of these partners bind to vigilin's carboxyterminus, and the two most C-terminal KH domains of the protein, KH13 and KH14, represent the main mRNA-binding interface. Since the nuclear functions of vigilins in particular are not conserved, we outline a model for the basal functions of vigilins, as well as those which were acquired during the transition from unicellular organisms to metazoa. WIREs RNA 2017, 8:e1448. doi: 10.1002/wrna.1448 For further resources related to this article, please visit the WIREs website.

An RNA-centric dissection of host complexes controlling flavivirus infection

“…Our results combined with the known role of RRBP1 and vigilin in translation of cellular mRNAs 32,33 suggests that the RBPs stimulate viral RNA replication, at least partially, by promoting translation of the viral polyprotein. Aside from translation, both vigilin and RRBP1 can also act on the stability of their target mRNAs 34,35 .…”

A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development

“…For some, such as the KSR protein, all four of its KH domains contribute to RNA binding (Hollingworth et al, 2012). For many others, such as the vigilin and ZBP1 proteins, RNA binding is conferred by a specific subset of KH domains (Nicastro et al, 2017;Nicastro et al, 2015;Cheng and Jansen, 2017). Our results provide evidence that the Bicc1 N-terminal region functions similarly to the latter category of multi KH-containing RNA-binding domains.…”

Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3′UTR element in CSF-1R mRNA

“…We first confirmed that translational repression of target mRNAs by vigilin ( Figure 1 ). It is known that vigilin binds a large number of mRNAs (estimated 700 mRNAs; [12] ). We demonstrate that vigilin directly interacts with the pyrimidine-rich element in the CSF-1R mRNA 3′UTR, and requires the full-length 69 nt for stable binding ( Figure 2 ).…”

“…Data on its role in cancer and the underlying mechanism is still limited. Further, it is recognized that while many of vigilin's known actions occur in the cytoplasm, vigilin's nuclear functions are less well understood [12] .…”