Long non-coding RNA prevents the death of maturing red blood cells

The main function of RNA was identified early on as being a template – in the form of messenger RNA that reflects the encoding of genes in DNA – for the construction of proteins. A few other forms of RNA were also recognized as playing a well-defined but subsidiary role in this process. However, research within the past five years has established that only 10 to 20% of RNA transcribed from DNA actually serves as a template for proteins.

The function of much of the remaining transcribed RNA is generally unknown. Many of these RNAs are short, with only a few tens of nucleotides, such as microRNA (miRNA). About 1000 different forms of miRNA have beein identified in the human genome, and the effective role of many of these has been discovered.

Longer forms of non-coding RNA, having more that 200 nucleotides, are known simply as long non-coding RNA (lncRNA). Only about 100 have been studied in mammalian tissues so far. The function of only a few of these has been determined. For example, one type is important in regulating stem cells during embryonic development.

Now another lncRNA has been found to play an important role in the maturation of red blood cells.

Long non-coding RNA prevents the death of maturing red blood cells

A long non-coding RNA (lncRNA) regulates programmed cell death during one of the final stages of red blood cell differentiation, according to Whitehead Institute researchers. This is the first time a lncRNA has been found to play a role in red blood cell development and the first time a lncRNA has been shown to affect programmed cell death.

The medical term for red blood cells is erythrocytes. The process in which erythrocytes are derived from their progenitors is erythropoiesis, and it requires the protein erythropoietin (EPO). (Erythros is Greek for “red”.)

The function of EPO is to prevent cell death (apoptosis) during erythropoiesis. Apoptosis is a problem, because erythropoiesis involves expulsion of the cell nucleus from the cell. (Erythrocytes are the only important human cell type that lack a nucleus.) This ejection process is similar to what occurs during apoptosis. It turns out that the type of lncRNA studied in the present research (called lncRNA-EPS) can also inhibit apoptosis. Further, the way that lncRNA-EPS inhibits apoptosis is by inhibiting expression of the Pycard gene for a pro-apoptotic protein.

In fact, the research showed that lncRNA-EPS can inhibit apoptosis during erythropoiesis even when EPO is not present, yet EPO by itself cannot inhibit apoptosis if lncRNA-EPS isn’t expressed. Perhaps the way EPO inhibits apoptosis is via expression of lncRNA-EPS.

However, there may be a downside to the activity of lncRNA-EPS. In some forms of leukemia (and other cancers), apoptosis does not occur when it should. Further research will be needed to determine whether excessive expression of lncRNA-EPS is a factor in leukemia, and if so, whether suppression of lncRNA-EPS may be a way to control leukemia.

Further reading:

Non-coding RNAs Halt Cell Death

Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation

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