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Studying sperm to understand gene regulation

7 June 2013

Drosophila testes containing developing sperm, stained blue
Drosophila testes containing developing sperm, stained blue

New research by Dr Helen White-Cooper (Reader at the School of Biosciences, Cardiff University) has revealed a critical mechanism controlling gene expression during sperm production.

Different cell types in animals have distinct structures and functions, despite them all containing the same set of genes.  These specialisms are produced because each cell uses (or activates) only a subset of all the genes in the genome.  Sperm are particularly highly specialised, and their production involves activation of many genes not used in any other part of the body.  Indeed, 5-10% of all genes are expressed exclusively in sperm precursor cells, known as spermatocytes, where they function to make structures not found in other cells (e.g. the acrosome, a bag of enzymes used by the sperm to get into the egg).

The critical question is how are these testis-specific genes activated in the spermatocytes, and equally importantly, how they are kept off in other cell types?

To address this fundamental problem, Dr White-Cooper has been working with fruit flies (Drosophila melanogaster) and has previously shown that a protein complex known as tMAC (for testis meiotic arrest complex) is exclusively produced in spermatocytes and directs the production of RNA from the testis-specific genes. In a new study, Dr White-Cooper has shown that a factor (Nxt1) known to be critical for moving RNAs from the nucleus to the cytoplasm also works to help tMAC produce the testis-specific RNAs.  This is a surprising finding which demonstrates a new cell-type specific role for a ubiquitous factor best known for a different role in other cell types. Males that lack Nxt1 function, like tMAC mutants, are completely sterile.

Dr White-Cooper explains “Our findings are particularly unexpected and interesting because every cell uses Nxt1 to get RNAs out of its nucleus, but this ability of Nxt1 to direct RNA production had not been discovered before.  The finding that only some RNAs (those made by tMAC) are affected by loss of Nxt1, shows that a general cellular pathway can have a very specific effect in individual cell types.  We suggest that Nxt1 might be particularly important in sperm production because so many genes have to switch from an "off" state to an "on" state in this process; feedback using Nxt1 could promote this switch”.