Waking the sleepers: lincRNA overexpression compromises DHX36 activity and global protein synthesis
- 1Department of Gene Expression, Laboratory of RNA Processing, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, P
Abstract
Transposable element-derived long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as context-dependent regulators of gene expression; however, the functional consequences of their ectopic activation in somatic cells remain poorly understood. We previously showed that U7 snRNA represses a subset of LTR12-associated lincRNAs, including lnc-ARRDC4-1 and lnc-ADCYAP1-2, two testis-enriched lincRNAs with minimal expression in somatic cells. Here, we examined the consequences of their increased expression in somatic cells. We showed that overexpression of either lincRNA led to common transcriptomic changes, proteomic changes, impaired migration, altered adhesion and proliferation, and a ~50% reduction in protein synthesis. Furthermore, we identified lnc-ARRDC4-1 as an upstream regulator of lnc-ADCYAP1-2 transcription. Downstream of this event, lnc-ADCYAP1-2 interacts with the RNA helicase DHX36, a regulator of G-quadruplex-containing mRNAs. lnc-ADCYAP1-2 activation reduces DHX36 protein levels, which is accompanied by decreased protein output from a subset of DHX36 mRNA targets. At the cellular level, these effects correlate with cellular disfunction and altered global translation. Our results suggest a lnc-ARRDC4-1:lnc-ADCYAP1-2:DHX36 regulatory cascade linking the derepression of LTR12-containing lincRNAs to reduced protein synthesis and altered cellular processes in somatic cells.
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BibTeX
@misc{pasieka2026waking,
title = {{Waking the sleepers: lincRNA overexpression compromises DHX36 activity and global protein synthesis}},
author = {R. Pasieka and P. Plewka and E. Vitale and I. Kapuscinska and M. Bajczyk and D. Bielewicz and T. Skrzypczak and K. Gawade and B. Koch and A. Ciarrocchi and K. D. Raczynska},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.28.735068},
url = {https://www.biorxiv.org/content/10.64898/2026.06.28.735068v2},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Waking the sleepers: lincRNA overexpression compromises DHX36 activity and global protein synthesis
AU - R. Pasieka
AU - P. Plewka
AU - E. Vitale
AU - I. Kapuscinska
AU - M. Bajczyk
AU - D. Bielewicz
AU - T. Skrzypczak
AU - K. Gawade
AU - B. Koch
AU - A. Ciarrocchi
AU - K. D. Raczynska
PY - 2026
DA - 2026/06/28
PB - bioRxiv
DO - 10.64898/2026.06.28.735068
UR - https://www.biorxiv.org/content/10.64898/2026.06.28.735068v2
AB - Transposable element-derived long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as context-dependent regulators of gene expression; however, the functional consequences of their ectopic activation in somatic cells remain poorly understood. We previously showed that U7 snRNA represses a subset of LTR12-associated lincRNAs, including lnc-ARRDC4-1 and lnc-ADCYAP1-2, two testis-enriched lincRNAs with minimal expression in somatic cells. Here, we examined the consequences of their increased expression in somatic cells. We showed that overexpression of either lincRNA led to common transcriptomic changes, proteomic changes, impaired migration, altered adhesion and proliferation, and a ~50% reduction in protein synthesis. Furthermore, we identified lnc-ARRDC4-1 as an upstream regulator of lnc-ADCYAP1-2 transcription. Downstream of this event, lnc-ADCYAP1-2 interacts with the RNA helicase DHX36, a regulator of G-quadruplex-containing mRNAs. lnc-ADCYAP1-2 activation reduces DHX36 protein levels, which is accompanied by decreased protein output from a subset of DHX36 mRNA targets. At the cellular level, these effects correlate with cellular disfunction and altered global translation. Our results suggest a lnc-ARRDC4-1:lnc-ADCYAP1-2:DHX36 regulatory cascade linking the derepression of LTR12-containing lincRNAs to reduced protein synthesis and altered cellular processes in somatic cells.
ER -