New Delhi, Nov. 7 th (India Science Wire): The process by which the mRNA codes for a particular
protein is known as translation. It is the final step in which an mRNA carrying information from
DNA synthesises proteins. It is a necessary process performed by almost all living cells, leaving
erythrocytes (Reb Blood Cells or RBCs), which are believed to be the only exception. A research
team led by Sandeep M Eswarappa, Associate Professor, Department of Biochemistry, Indian
Institute of Science, Bengaluru, has identified that mature human RBCs can also make their
proteins.
Unlike other cells of the human body, RBCs do not have a nucleus. They have a long lifespan of
nearly 115-120 days. Though initially thought to be mere bags of proteins, these cells are now
metabolically active and have a comprehensive collection of mRNAs, micro RNAs, and other
long non-coding RNAs. As these cells perform metabolic functions, these proteins must be
replenished. But, proteins rarely remain stable for 120 days, the lifespan of an RBC. The
researchers discovered the presence of active translation in these cells.
Study involved techniques such as metabolic labelling using [ 35 S]-methionine and
RiboPuromycylation to study this process in erythrocytes. With the help of electron microscopy
the researchers could see actively translating ribosomes – polysomes – and the translation
machinery, in these cells. Isolation of polysomes and RNA-sequencing of the mRNAs associated
with it provided information on the proteins that were being synthesised. The analysis
identified HBA (α-globin) and HBB (β-globin), the components that make haemoglobin, that are
primarily synthesised in these cells. Furthermore, it was also observed that mature erythrocytes
showed reduced expression of globin proteins (α- and β-) when treated with translation
inhibitors.
The Researchers believe that this study would open new avenues to treat group of disorders
like haemoglobinopathies, which happen due to abnormal production or structure of the
haemoglobin molecule. Currently, the treatment for these disorders includes targeting
precursors of the blood cells from bone marrow, which is quite challenging. By discovering the
translation process in these cells, they can now proceed to regulate the protein expression
directly in these highly accessible cells, making developing therapeutic strategies for such
disorders easier.
The study has been published in Molecular Biology of the Cell journal.
