miR-1289 and “Zipcode”-like Sequence Enrich mRNAs in Microvesicles

Abstract

Despite intensive studies, the molecular mechanisms by which the genetic materials are uploaded into microvesicles (MVs) are still unknown. This is the first study describing a zipcode-like 25 nucleotide (nt) sequence in the 3′-untranslated region (3′UTR) of mRNAs, with variants of this sequence present in many mRNAs enriched in MVs, as compared to their glioblastoma cells of origin. When this sequence was incorporated into the 3′UTR of a reporter message and expressed in a different cell type, it led to enrichment of the reporter mRNA in MVs. Critical features of this sequence are both a CUGCC core presented on a stem-loop structure and a miRNA-binding site, with increased levels of the corresponding miRNA in cells further increasing levels of mRNAs in MVs.

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

“…The molecular mechanism by which nucleic acids are uploaded into exosomes is emerging. A recent study suggests that mRNA sorting into glioblastoma-derived MVs may be directed through the interaction between a "zipcode"-like sequence, present in the transcripts, and miR-1289 [40].…”

Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state

“…Interestingly, vesiculation is known to lead to selective enrichment of some bioactive molecules but not others in the EV cargo, and the nature, mechanisms and consequences of these combinatorial processes encompassing large numbers of molecular species involved are still poorly understood [21,31,32].…”

Therapeutic and diagnostic applications of extracellular vesicles

“…t-RNA, Y-RNA, vault RNA, etc.) are enriched or underrepresented in EVs compared to their respective parent cells [36][37][38][39][40][41]. Based on these observations it is generally accepted that the composition of EVs is, at least partially, actively regulated by the parent cell [42], albeit that the mechanisms and associated key players regulating this cargo sorting remain largely elusive to date [38,[43][44][45][46].…”

“…This enrichment could even be further enhanced when miR-1289 was overexpressed in the producing cell [39]. Regarding miRNA sorting, Koppers-lalic et al discovered that 3'-uridylated miRNAs are enriched in human B cell-derived EVs [45].…”