Abstract P385: Sex-specific Long Non-coding Gene Expression In Rat Nephron Segments

Abstract

Transcriptomic and proteomic approaches have identified electrolyte transporters, channels and claudins with sex-specific expression along the nephron which adapt to physiological stressors in a sex-specific manner to maintain proper fluid and electrolyte homeostasis. Yet, less is known how long non-coding gene expression in specific nephron segments differs between sexes. We performed polyA-independent RNA-seq on manually isolated proximal tubule (PT) and medullary thick ascending limb (mTAL) from 6-7-week-old male and female Dahl salt sensitive rats. Sex specific gene expression differences [log2(fold change) ≥ 0.5 or ≤ -0.5; p adj ≤ 0.05] are summarized in the table. More sex-specific differences of both protein coding and lncRNA genes were detected in PT compared to mTAL. lncRNAs were less likely to demonstrate sex-specific differences than protein coding genes (p=2.59e-12 for PT and p=5.68e-3 for mTAL). Rare lncRNAs were expressed in one sex or the other (sex-exclusive). An interesting example is ENSRNOG00000069167 and ENSRNOG00000063718 which are transcribed on opposite strands from an overlapping sequence in male or female mTAL, respectively. Multiple sex-exclusive lncRNAs were colocalized with protein coding genes significantly enriched in the same sex, suggesting they may be co-regulated within a specific chromatin domain. For example, ENSRNOG00000068738 was exclusively expressed in male PT and is colocalized in a ~560-kbp region with Pcnx1 and Sipa1l1, both of which were also enriched in male PT. Collectively, these results extend our understanding of sex-specific gene expression differences in these nephron segments to include long non-coding genes.