Long non-coding RNA (lncRNA) sequences, so named for what they cannot do — namely, code for proteins — are piquing the interests of researchers. In an article in Genes and Development, Hu et al. report that lncRNAs play an important role in regulating red blood cell production in mice. In particular, the lncRNA sequences that they studied seem to inhibit apoptosis, or cell death, an important factor in regulating red blood cell production.
Researchers found that lncRNAs are actively involved in several biological processes including maintenance of pluripotency in stem cells, development, cancer metastasis, and now erythropoiesis (red blood cell production, particularly during development) can be added to the list. LncRNAs are unique in that they are able to regulate the expression of certain genes in a variety of ways. The authors write,
Interestingly, mechanistic studies revealed that unlike small RNAs, such as microRNAs, lncRNAs can regulate gene expression via diverse mechanisms…such as chromatin modification, enhancing transcription, and promoting mRNA degradation. Collectively, these observations revealed that lncRNAs are a novel class of regulatory factors in modulating gene expression under various biological processes.
In the study, the authors developed a robust method for identifying and characterizing the expression of lncRNAs during erythropoiesis. Their studies showed that more than four hundred lncRNAs are expressed during erythropoiesis. One segment of RNA in particular, lincRNA-EPS, affects cell differentiation and apoptosis (cell death) by affecting the expression of other genes that promote apoptosis.
These findings have two important implications. First, non-coding regions of the genome were assumed to be leftover evolutionary relics that no longer play a functional role. The assumption was not due to extensive studies of non-coding regions of the genome, but rather to a commitment to what is known as the central dogma of molecular biology: DNA is transcribed into RNA and RNA is translated into amino acids to make proteins. This was considered the primary purpose of DNA. The non-coding regions were assumed to have no function, and were dismissed as the natural consequence of genetic “junk” accumulating over time. This paper is one among an accumulating corpus of papers discussing new and interesting functions of the non-coding regions of the genome. (See The Myth of Junk DNA by Jonathan Wells for a history of “junk” DNA and additional references describing the function of so-called “junk” DNA. See here for a discussion on the regulatory role of introns.)
Secondly, cellular processes are not only highly complex, but highly regulated. As the authors of this study point out, “these results revealed a novel layer of regulation of erythroid cell differentiation and apoptosis by a lincRNA.” When we consider that many aspects of the cell are highly regulated, we find that the cell operates like a factory with an intricately woven network of processes rather than a hodge-podge of functioning and non-functioning pieces of the kind you might expect to result from a randomly driven evolutionary process. With every discovery of additional layers of complexity and regulation in the cell, we see the hallmarks of engineered or designed processes.