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The CF Im protein complex globally controls the length of messenger RNAs

In a cell, the genetic information is first copied into messenger RNAs (mRNAs), which are then translated into proteins. The longer the mRNA molecules persist in the cell, the more proteins can be synthesized. In rapidly dividing cells such as tumor cells, shorter mRNAs are believed to be more stable, generating higher levels of proteins, including those that promote cancer. In the journal Cell Reports, scientists lead by Prof. Zavolan and Prof. em. Keller, report about the control of mRNA length by the protein complex CF Im.

Complex mechanisms control protein synthesis and cell growth. The life-time of messenger RNAs determines how many protein molecules are produced from these mRNAs. mRNA life-time can be regulated in many ways, among which by regulatory proteins that bind regions of the mRNAs that do not contain the information for protein synthesis. Frequently, these regulatory proteins destabilize the mRNAs, and therefore shorter mRNAs, that lack these protein-binding sites, generate more proteins. Scientists lead by Prof. Zavolan and Prof. em. Keller, have recently discovered that the site of cleavage and thus the length of the mRNAs is defined by the protein Mammalian Cleavage Factor I (CF I_m).

Short mRNAs due to reduced quantities of CF I_m

Messenger RNAs, that serve as templates for protein synthesis are produced from building blocks, which are added to a growing chain one at a time, in a process that is called polymerization. The instructions for when to stop are also written in the DNA. By binding to specific sites on the growing RNA chain, the protein complex CF I_m marks the spot at which “molecular scissors” are recruited to cut the chain and stop its elongation. Human genes typically have not one, but multiple sites at which protein complexes can be recruited to stop the elongation of the mRNA. Which of these sites ends up being used depends on the concentration of CF I_m. The researchers could demonstrate that in cells with little CF I_m, almost all genes produce the shorter mRNA variants.  Also affected was the RNA of a protein involved in the development of breast and prostate cancers. Thus, through extensive analyses of the entire “transcriptome” with a newly developed method, the scientists discovered parts of the mechanism that controls the mRNA length and protein production in human cells.

New link revealed

Shorter mRNAs were recently linked to oncogene activation. In the current study, the research group from the Biozentrum identified a mechanism through which mRNA length can be globally regulated, namely through the concentration of the CF I_m. The scientists now plan to more closely investigate the functions of the different members of this protein complex as well as other proteins that, through the interaction with CFI_m, regulate mRNA length.

Original article:
Georges Martin, Andreas Gruber, Walter Keller and Mihaela Zavolan (2012). Genome-wide Analysis of Pre-mRNA 3´End Processing Reveals a Decisive Role of Human Cleavage Factor I in the Regulation of 3´UTR Length. Cell Reports 1(6), 753-763

Contact: Communications, Katrin Bühler