Unwinding the roles ofRNAhelicaseMOV10

Abstract

MOV10 is an RNA helicase that associates with the RNA-induced silencing complex component Argonaute (AGO), likely resolving RNA secondary structures. MOV10 also binds the Fragile X mental retardation protein to block AGO2 binding at some sites and associates with UPF1, a principal component of the nonsense-mediated RNA decay pathway. MOV10 is widely expressed and has a key role in the cellular response to viral infection and in suppressing retrotransposition. Posttranslational modifications of MOV10 include ubiquitination, which leads to stimulation-dependent degradation, and phosphorylation, which has an unknown function. MOV10 localizes to the nucleus and/or cytoplasm in a cell type-specific and developmental stage-specific manner. Knockout of Mov10 leads to embryonic lethality, underscoring an important role in development where it is required for the completion of gastrulation. MOV10 is expressed throughout the organism; however, most studies have focused on germline cells and neurons. In the testes, the knockdown of Mov10 disrupts proliferation of spermatogonial progenitor cells. In brain, MOV10 is significantly elevated postnatally and binds mRNAs encoding cytoskeleton and neuron projection proteins, suggesting an important role in neuronal architecture. Heterozygous Mov10 mutant mice are hyperactive and anxious and their cultured hippocampal neurons have reduced dendritic arborization. Zygotic knockdown of Mov10 in Xenopus laevis causes abnormal head and eye development and mislocalization of neuronal precursors in the brain. Thus, MOV10 plays a vital role during development, defense against viral infection and in neuronal development and function: its many roles and regulation are only beginning to be unraveled.

Sequestration of LINE‐1 in cytosolic aggregates by MOV10 restricts retrotransposition

“…The role of MOV10 in inhibiting retrotransposition in human tissue culture was discovered almost 10 years ago (Goodier et al , 2012). Since then, multiple reports have corroborated this seminal function, where it participates either directly or along with protein partners in curbing retrotransposition (Arjan‐Odedra et al , 2012; Li et al , 2013; Skariah et al , 2017; Choi et al , 2018; Warkocki et al , 2018; Nawaz et al , 2022). Here, we discover cytosolic‐body formation induced by MOV10 as a line of defense for sequestration of L1 RNP particles to prevent deleterious L1 retrotransposition in mESCs.…”

“…Given the plethora of functions MOV10 has been implicated in, it is not surprising that mechanisms have evolved to regulate its expression and activity (Nawaz et al , 2022). Posttranslational modification of MOV10 occurs via ubiquitination in neuron cultures derived from rat hippocampus resulting in its degradation (Banerjee et al , 2009).…”

“…Posttranslational modification of MOV10 occurs via ubiquitination in neuron cultures derived from rat hippocampus resulting in its degradation (Banerjee et al , 2009). Moreover, phosphorylation and acetylation of MOV10 have been observed to occur in human cancer cell lines and speculated to regulate its activity and levels (Nawaz et al , 2022). Data presented here, to the best of our knowledge, are a first to unveil miRNA‐mediated posttranscriptional regulation of Mov10 expression.…”

Genome-wide analysis of RNA-binding protein co-expression with alternative splicing events in acute respiratory distress syndrome following hematopoietic stem cell transplantation

“…[26–28] MOV10 is widely expressed, has antiviral and retrotransposition-blocking activities, and is involved in normal mRNA metabolism and translation, particularly in the IFN-mediated immunity against viral pathogens. [29,30] The results suggest that patients with HSCT-ARDS have a reduced ability to resist and clear viruses. Furthermore, type 1 IFN can activate a variety of antiviral factors in host cells.…”

A Systematic Identification of RBPs Driving Aberrant Splicing in Cancer

“…This group is characterized by the high presence of altered CELF4 and MOV10 among its samples. Both genes have been related to cancer development (38,39).…”