Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs

Matthew Hangauer, Ian W. Vaughn, and Michael T. McManus
Source | Archive.is

In 2013, Matthew Hangauer and Ian Vaughn published a study on lincRNAs, finding an even higher level of transcription than reported by ENCODE:

Here, by analyzing a large set of RNA-seq data, we found that >85% of the genome is transcribed,

They looked at a specific class of RNA transcripts known as lincRNAs and found them to be highly functional:

A key question in the field is whether these intergenic transcripts are functional or transcriptional noise. We found that the lincRNAs we identified have many characteristics that are inconsistent with noise, including specific regulation of their expression, the presence of conserved sequence and evidence for regulated processing. Furthermore, these lincRNAs are strongly enriched with intergenic sequences that were previously known to be functional in human traits and diseases...

At a threshold of one RNA-seq read, we observed reads mapping to 78.9% of the genome and, if additional evidence of transcription is taken into account including the full structures of known genes, spliced ESTs and cDNAs, we found evidence that 85.2% of the genome is transcribed (Figure 1A). This result closely agrees with the recently published findings from the ENCODE project in which evidence for transcription of 83.7% of the genome was uncovered. Interestingly, even with 4.5 billion mapped reads, we observe an increase in genomic coverage at each lower read threshold implying that even more read depth may reveal yet higher genomic coverage...

These observations clearly demonstrate that the human genome is pervasively transcribed, and that lincRNAs make up an extremely common class of intergenic transcripts...

In order to minimize any potential contamination of the lincRNA catalog with protein coding transcripts, the filtering approach used was very aggressive. In fact, most previously annotated noncoding RNAs failed to pass our filters and were therefore excluded from the lincRNA catalog...

Replicates of each tissue type strongly clustered together, indicating that lincRNA differential expression is indeed reproducibly tissue-specific, supporting specific regulation of lincRNA expression.