Expression of transcribed ultraconserved regions of genome in rat cerebral cortex

Abstract

Emerging evidence indicates that 481 regions of the genome (>200 bp) that actively transcribe noncoding RNAs shows 100% homology between humans, rats and mice. These transcribed ultraconserved regions (T-UCRs) are thought to control the essential regulatory functions basic for life in rodents and mammals. Using microarray analysis, we presently show that 107 T-UCRs are actively expressed in adult rat cerebral cortex. They are grouped into intragenic (61) and intergenic (46) based on their genic location. Interestingly, 10 T-UCRs are expressed at unusually high levels in cerebral cortex. Additionally, many T-UCRs also showed cogenic expression. We further analyzed the correlation of intragenic T-UCRs with their host protein coding genes. Surprisingly, most of the expressed intragenic T-UCRs (54 out of 61) displayed a negative correlation with their host gene expression. T-UCRs are thought to control the splicing and transcription of the protein-coding genes that host them and flank them. Bioinformatics analysis indicated that the protein products of majority of these genes are nuclear in localization, share protein domains and are involved in the regulation of diverse biological and molecular functions including metabolism, development, cell cycle, binding and transcription factor regulation. In conclusion, this is the first study to shows that many T-UCRs are expressed in rodent brain and they might play a role in physiological brain functions.

Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation

“…By combining large-scale genome-wide expression analysis and in situ hybridization detection, several groups showed that T-UCEs are differentially expressed in both time and space with highly restricted expression in selected regions of the mammalian embryo [ 117 – 119 ]. High-resolution screening of RNA sequence signals derived from annotated ultraconserved sequences revealed that 76 UCEs are actively transcribed and specifically enriched in the nervous system of developing brain at embryonic day E14.5 [ 119 ]. In particular, T-UC.77, T-UC.338, T-UC.377, and T-UC.359 show dynamic expression profiles increasing during E12.5–E18.5 of mouse brain development.…”

“…3 , top panel). Of note, some T-UCEs remain expressed in adult brain, functioning in homeostasis in the cerebral cortex [ 119 ].

Fig.

…”

Ischemic Stroke Alters the Expression of the Transcribed Ultraconserved Regions of the Genome in Rat Brain

“…3 Total RNA was extracted from peri-infarct cortex at 3h, 6h and 12h of reperfusion and hybridized to Arraystar lncRNA microarrays (n=3/group). 2 Expression data were analyzed with GeneSpring GX V11.0 software. Post-ischemic changes in the expression of T-UCRs and their host gene mRNAs were validated by real-time PCR (n=4/group).…”

“…Genomic coordinates and the exon, intron and exon-intron overlap of T-UCRs were determined by bioinformatics. 2 Molecular functions and biological process networks of up/downstream and host genes of T-UCRS was determined with PANTHER algorithm. 2…”

“…4 T-UCRs are considered as a subclass of lncRNAs and their extreme conservation might be related to the strict negative purifying selection that is vital for life in mammals. 4,5 Although T-UCRs are expressed at high levels in adult brain and many of them alter significantly in various diseases, 2,5–7 their physiologic significance is not known. To understand if an acute brain injury modulates T-UCRs, we presently investigated their temporal expression profiles following transient focal ischemia.…”