tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model

Abstract

tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the fetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5' tRNA halves from tRNA Gly , tRNA Glu , tRNA Val and tRNA Lys are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal-interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 hours after MIA and are suppressed thereafter. A group of 5' tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.

RNA interference mediates RNA toxicity with parent-of-origin effects inC. elegansexpressing CTG repeats

“…Recently, a maternal parent-of-origin effect was observed in the transmission of small RNA-based endoderm development phenotypes and RNAi machinery defects 57,69,70 . In mammals, the presence of small RNAs from maternal origin was shown in human and mouse cord blood [71][72][73][74][75] .…”

tRNA-derived fragments: Mechanisms underlying their regulation of gene expression and potential applications as therapeutic targets in cancers and virus infections

“…Preparatory bioinformatic analysis suggests that tRFs have sufficient sequence complementarity with endogenous mRNAs and thus may play a potential role in posttranscriptional regulation 19 , 20 . As one kind of sncRNA with a length less than 30 nt, it seems logical to conclude that tRFs have functions similar to those of miRNAs 21 , 22 .…”

Regulatory roles of tRNA-derived RNA fragments in human pathophysiology

“…In hematopoietic stem cells, downregulated PUS7 leads to the upregulation of 5 0 -tiRNAs. 95 Using deep sequencing data analysis, Su et al 96 have reported differential expression of tRFs in placenta/decidua, fetal brain, and fetal liver. 96 Furthermore, the expression of tRFs changes dynamically as embryonic development progress.…”