The RNA‐binding protein hnRNPU regulates the sorting of microRNA‐30c‐5p into large extracellular vesicles

Abstract

Jansen (2020) The RNAbinding protein hnRNPU regulates the sorting of microRNA-30c-5p into large extracellular vesicles,

Biogenesis of RNA-containing extracellular vesicles at endoplasmic reticulum membrane contact sites

“…Although packaging of exRNAs in EVs is known to be a selective process that leads to the enrichment of certain exRNAs in EVs (Cha et al, 2015;Lee et al, 2019;Lin et al, 2019;Lu et al, 2017), the mechanisms by which this packaging occurs is poorly understood. RNA-binding proteins appear to play a major role in this process, likely controlling both stability and sorting of the RNAs (Deng et al, 2020;McKenzie et al, 2016;Santangelo et al, 2016;Shurtleff et al, 2016;Villarroya-Beltri et al, 2013;Zietzer et al, 2020). We and others identified argonaute 2 (Ago2) and other RISC complex proteins as potent mediators of miRNA sorting into EVs (Bukong et al, 2014;Clancy et al, 2019;Mantel et al, 2016;McKenzie et al, 2016;Melo et al, 2014).…”

“…While RBPs are known to be important for the transport of RNAs into EVs (Leidal et al, 2020;Lin et al, 2019;Santangelo et al, 2016;Shurtleff et al, 2016;Villarroya-Beltri et al, 2013;Zietzer et al, 2020), it has been unclear how the RBP-RNA complexes are recruited to membranes for incorporation into EVs. Recent work has shown that two membraneless organelles that are comprised of RBP-RNA complexes -processing bodies and stress granules -form contacts with the ER (Lee et al, 2020).…”

“…Other studies have shown that miRNAs with specific sequence motifs (i.e., GGAG and GGCU) are recognized and selectively sorted into EVs by heterogenous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and RNA-interacting protein SYNCRIP (Santangelo et al, 2016;Villarroya-Beltri et al, 2013). In addition, the RNA-binding protein Y-box I (YBX-1) is suggested to be involved in the packaging of mRNAs, miRNAs and other exRNAs into EVs by recognizing secondary rather than primary RNA sequence motifs (Kossinova et al, 2017;Shurtleff et al, 2016;Shurtleff et al, 2017;Zietzer et al, 2020).…”

Small extracellular vesicles with LncRNA H19 “overload”: YAP Regulation as a Tendon Repair Therapeutic Tactic

“…Most of the RNA transfer to specific cellular locations relies on RBPs, which can travel along the cytoskeleton ( Di Liegro et al., 2014 ; Eliscovich et al., 2013 ). RBPs, including HuR ( Mukherjee et al., 2016 ), hnRNP A2/B1( Villarroya-Beltri et al., 2013a ), hnRNPK ( Leidal et al., 2020 ), hnRNPU ( Zietzer et al., 2020 ), and scaffold-attachment factor B1(SAFB) ( Leidal et al., 2020 ), have been found to be involved in RNA packaging into EVs. Most of the current research is focused on the observation of this phenomenon and exploration of the mechanism, but very little research has been done to exploit these mechanisms as a tool for nucleic acid delivery.…”

RNAs on the Go: Extracellular Transfer in Insects with Promising Prospects for Pest Management

“…Two potential RNA selective sorting mechanisms have been proposed in mammals. First, miRNAs packaged into EVs were demonstrated to contain specific nucleotide motifs with which specific ribonucleoproteins interact to allow selective sorting [ 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 ]. Moreover, several membrane proteins involved in EV biogenesis are also involved in selective miRNA sorting [ 50 , 220 , 221 , 222 ].…”