Global Intersection of Long Non-Coding RNAs with Processed and Unprocessed Pseudogenes in the Human Genome

Abstract

Pseudogenes are abundant in the human genome and had long been thought of purely as nonfunctional gene fossils. Recent observations point to a role for pseudogenes in regulating genes transcriptionally and post-transcriptionally in human cells. To computationally interrogate the network space of integrated pseudogene and long non-coding RNA regulation in the human transcriptome, we developed and implemented an algorithm to identify all long non-coding RNA (lncRNA) transcripts that overlap the genomic spans, and specifically the exons, of any human pseudogenes in either sense or antisense orientation. As inputs to our algorithm, we imported three public repositories of pseudogenes: GENCODE v17 (processed and unprocessed, Ensembl 72); Retroposed Pseudogenes V5 (processed only), and Yale Pseudo60 (processed and unprocessed, Ensembl 60); two public lncRNA catalogs: Broad Institute, GENCODE v17; NCBI annotated piRNAs; and NHGRI clinical variants. The data sets were retrieved from the UCSC Genome Database using the UCSC Table Browser. We identified 2277 loci containing exon-to-exon overlaps between pseudogenes, both processed and unprocessed, and long non-coding RNA genes. Of these loci we identified 1167 with Genbank EST and full-length cDNA support providing direct evidence of transcription on one or both strands with exon-to-exon overlaps. The analysis converged on 313 pseudogene-lncRNA exon-to-exon overlaps that were bidirectionally supported by both full-length cDNAs and ESTs. In the process of identifying transcribed pseudogenes, we generated a comprehensive, positionally non-redundant encyclopedia of human pseudogenes, drawing upon multiple, and formerly disparate public pseudogene repositories. Collectively, these observations suggest that pseudogenes are pervasively transcribed on both strands and are common drivers of gene regulation.

Classification and function of small open reading frames

“…In turn, short CDSs could integrate, fuse and grow into canonical proteins. This mechanism would increase the number of genes through evolution, and although such an increase can be appreciated (Figure 1) creation of new canonical ORFs is counter-balanced by conversion of canonical ORFs into shorter isoforms, pseudogenes, and perhaps lncRNAs 111 , as well as the random disappearance of intergenic ORFs by transcription and ATG codon loss. B) The Scl family of lncORFs show loose amino acids sequence conservation, but their structure and molecular function is conserved 13,20 .…”

Genome‑wide integrated analysis demonstrates widespread functions of lncRNAs in mammary gland development and lactation in dairy goats

“…Long noncoding RNAs are a class of mRNA-like transcripts that have been operationally defined as mostly 5′-capped, polyadenylated and spliced, exhibiting lengths greater than 200 nt (nucleotide), and lacking ORFs (open reading frames) [1]. According to genomic localization of these RNAs with respect to nearby mRNAs, lncRNAs are divided into five loose categories: (1) sense lncRNAs, overlapped with one or more exons from another transcript on the same strand; (2) antisense lncRNAs, overlapped with one or more exons from another transcript on the other strand; (3) bidirectional lncRNAs, which initiate a similar expression pattern to its nearing mRNA counterpart on the other strand; (4) intronic lncRNAs, overlapped with one or more introns in another transcript; (5) and intergenic lncRNAs (lincRNAs), located in the interval between two protein coding genes on the same strand [2,3]. Nevertheless, recent functional studies in mammals have found that lncRNAs serve as critical regulators in various biological processes by regulating gene expression at the epigenetic, transcription, and postttranscription levels.…”

Protein-Coding Genes’ Retrocopies and Their Functions

“…By generating two mouse strains with gene-trap insertions upstream of the retrocopy, the authors demonstrated relationships between the piRNA precursor, piRNA, and the parental gene levels, which clearly suggests a role of the retrocopy in Stambp regulation [149]. PiRNA clusters overlapping retrocopies were also found in other recent studies (e.g., [150,151]).…”