Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression

Proceedings of the National Academy of Sciences of the United States of America
Kalliopi StratigiCharalampos G Spilianakis

Abstract

Physiological processes rely on the regulation of total mRNA levels in a cell. In diploid organisms, the transcriptional activation of one or both alleles of a gene may involve trans-allelic interactions that provide a tight spatial and temporal level of gene expression regulation. The mechanisms underlying such interactions still remain poorly understood. Here, we demonstrate that lipopolysaccharide stimulation of murine macrophages rapidly resulted in the actin-mediated and transient homologous spatial proximity of Tnfα alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNFα locus and showed that their knockdown had opposite effects in Tnfα spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnfα alleles depended on pyruvate kinase muscle isoform 2 (PKM2) and T-helper-inducing POZ-Krüppel-like factor (ThPOK). This study suggests a role for lncRNAs in the regulation of somatic homologous spatial proximity and allelic expression control necessary for fine-tuning mammalian immune responses.

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Citations

Apr 12, 2016·Current Opinion in Genetics & Development·Eric F JoyceC-Ting Wu
Oct 6, 2016·Mechanisms of Ageing and Development·Kalliopi StratigiGeorge A Garinis
Sep 15, 2017·PloS One·Chrysoula StathopoulouCharalampos Spilianakis
Apr 6, 2019·Genetics·Pawel PiwkoChristos Delidakis
Nov 5, 2019·PloS One·Eralda SalatajCharalampos G Spilianakis
Sep 1, 2017·Cellular and Molecular Life Sciences : CMLS·Avinash SrivastavaRakesh K Mishra
Nov 4, 2020·RNA Biology·Katharina Walther, Leon N Schulte
May 15, 2021·Wiley Interdisciplinary Reviews. RNA·Nils Schmerer, Leon N Schulte

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