A computational biologist looks at how mRNA length changes during development.

I am always amazed by how we start as a fertilized egg and develop into a complex, multicellular organism. This feat occurs despite the fact that the DNA in every cell — even the most specialized ones — remains, for the most part, unchanged.

One method of regulating gene activity in differentiated, or specialized, cells is through the messenger RNA (mRNA), the code of which is translated to make proteins. For example, proteins and other RNAs can bind to the untranslated regions (UTRs) at the 5′ and 3′ ends of mRNAs to regulate mRNA stability and translation.

The constitution of the 3′ UTR itself can be regulated through alternative polyadenylation, whereby one of several possible UTR sites is cleaved, followed by the addition of adenosine-based molecules to its end. A broad shift in cleavage site choice — and thus 3′ UTR length — during mammalian development was recently described by Bin Tian and his team at the University of Medicine and Dentistry of New Jersey in Newark (Z. Ji et al. Proc. Natl Acad. Sci. USA 106, 7028–7033; 2009).

By analysing genomic data, they show that 3′ UTRs generally get longer during development and cell differentiation. The authors further show that most of the genes in which 3′ UTRs are lengthened are also those that are increasingly suppressed during differentiation, such as the genes for DNA replication and cell division.

These findings bring to the forefront an underappreciated mechanism of genetic regulation that is likely to be important for normal cell differentiation. It is fascinating how many steps of the central dogma (DNA to RNA to protein) are controlled. This seems to be how evolution has managed to take a relatively simple cell and multiply it to form the complex body plan of the human.

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