Abstract
Endogenous retroelements constitute almost half of the mammalian genome. Given that more than 60% of human genomic bases are transcribed, transcripts containing these retroelements may impact various biological processes. However, the physiological roles of most retroelement-containing transcripts are yet to be revealed. Here, we profiled the expression of retroelement-containing human transcripts during vaccination and found that vaccination upregulated transcripts containing only particular retroelements, such as the MLT-int element of endogenous retroviruses. MLT-int-containing transcripts were distributed mainly in the nucleus, suggesting their unique roles in the nucleus. Furthermore, we demonstrated that MLT-int RNA suppressed interferon promoter activity in the absence of immune stimuli. Based on these lines of evidence, we speculate a model of a role of the previously unnoticed MLT-int element in preventing excess innate immune activation after elimination of immune stimuli. Our results may emphasize the importance of retroelement-containing transcripts in maintaining host immune homeostasis.
Highlights
Endogenous retroelements constitute almost half of the mammalian genome [1]
We investigated the transcriptional landscapes of retroelement-containing human transcripts during immune stimulation by vaccination and revealed that vaccination did not change overall landscapes of retroelement-containing transcripts (Figure S1A,B)
Induction of specific retroelements after immune stimulation prompts us to speculate the roles of these MLT-int-containing transcripts in immune tuning
Summary
Endogenous retroelements constitute almost half of the mammalian genome [1]. Among them, endogenous retroviruses (ERVs) are fossil records of ancient retroviruses and occupy ~10% of the human genome [1]. A small number of distinct ERVs are strongly induced during B-cell activation, while ERVs are widely induced during B-cell transformation [5] These observations suggest that particular ERVs or ERV-containing transcripts may play roles in host immune tuning, and that dysregulation of such ERV expressions may contribute to pathological conditions. OOvveerraallll,, aa pprrooppoorrttiioonn ooff rreettrrooeelleemmeenntt--ccoonnttaaiinniinngg ttrraannssccrriippttss wweerree aallmmoosstt ccoommppaarraabbllee bbeettwweeeenn pprree-- aanndd ppoosstt--vvaacccciinnaattiioonn ((FFiigguurreeS1SA1,AB,)B. Amsessheonwgner iRnNFAig(umreRN3BA, )MwLaTs-iinnt-hceoncytationpinlagsmtra(FnisgcurirpetSs2wCe).rTe hdeissetrriebsuutletds smuagignelsyt tihnatthMeLnT-uicnlte-ucosnrtaeignairndgletsrasnoscf ritphtes plraeyseanuceniqouf eproollyeIi:Cn ,thwe hniulecleausp.rotein-coding GAPDH messenger RNA (mRNA) was in the cytoplasm (Figure S2C). These results suggest that MLT-intcontaining transcripts play a unique role in the nucleus
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