Protein synthesis in cells without a nucleus

Translation, or protein synthesis, is the final step in the central dogma of molecular biology, where an mRNA carrying information from DNA, synthesises proteins. It is an indispensable process that is performed by almost all living cells. An exception where translation was believed to be absent is erythrocytes (RBCs). Now, a team led by Sandeep M Eswarappa, Associate Professor at the Department of Biochemistry, has identified that mature human red blood cells can also make their own proteins.

What sets these red blood cells apart from the other cells of the human body is their anucleate nature and their long lifespan of 120 days. Though initially thought to be mere bags of proteins, these cells are metabolically active and harbour a wide repertoire of mRNAs, micro RNAs, and other long non-coding RNAs. Given that these cells perform metabolic functions, replenishment of these proteins is imperative. Proteins rarely are stable for 120 days. In this study, published in Molecular Biology of the Cell, the researchers have discovered the presence of active translation in these cells.

Techniques that detect de novo protein synthesis, such as metabolic labelling using ³⁵S-methionine and RiboPuromycylation, were employed to study this process in erythrocytes. Electron microscopy also revealed the presence of actively translating ribosomes – polysomes – and the translation machinery, in these cells. Isolation of polysomes and RNA-sequencing of the mRNAs associated with it shed light on the proteins that are being synthesised.  The analysis identified alpha globin and beta globin, the components that make haemoglobin – the oxygen carrying protein – that are primarily synthesised in these cells.

This study opens new avenues to treat diseases caused by abnormal haemoglobin, called haemoglobinopathies. Currently, the treatment for these disorders includes targeting precursors of the blood cells from bone marrow, which can be very challenging. By discovering the translation process in these cells, researchers can now proceed to regulate the protein expression directly in these highly accessible cells, making it easier to develop new therapeutic strategies for such disorders.

Reference:

Sangeetha Devi Kumar, Debaleena Kar, Md Noor Akhtar, Belinda Willard, Debadrita Roy, Tanweer Hussain, Purusharth I Rajyaguru, and Sandeep M Eswarappa; Evidence for low-level translation in human erythrocytes, Molecular Biology of the Cell, 22 September 2022; Vol. 33, No. 12

https://www.molbiolcell.org/doi/10.1091/mbc.E21-09-0437

Lab webpage:

https://sites.google.com/view/dr-sandeep-m-eswarappa/home