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How one gene leads to two proteins

Max Planck researchers discover a new mechanism that turns one gene into two proteins

Small proteins of the ubiquitin family work like molecular switches and regulate many cellular functions. Researchers at the Max Planck Institute for Biochemistry (MPIB) in Martinsried near Munich have now found that the Hub1 protein of this protein family has an important influence on protein synthesis: It influences how cells translate the information encoded in the genes. Thanks to Hub1, one gene can even provide the information for two proteins. This creates more proteins than there are genes. This mechanism could also influence protein production in humans and therefore have many effects on healthy as well as sick human cells.

Every cell has a large number of proteins that control vital functions. Each protein takes on special tasks that can, however, be changed by subsequent modifications to the proteins. Particularly fascinating are cases in which proteins are changed by the chemical attachment of small proteins of the ubiquitin family. Ubiquitin was discovered in the 1970s and is known as the label for degradation: proteins linked to ubiquitin can be crushed by a “cellular mill”.

Scientists in Stefan Jentsch's laboratory at MPIB identified and examined Hub1, an unusual member of the ubiquitin family. Although Hub1 has a similar structure to Ubiquitin and other family members, it works in a completely different way. Shravan Kumar Mishra, a postdoc at the MPIB, found that Hub1 binds tightly, but not chemically, to the highly conserved protein Snu66. This protein is part of a specific cellular machine (spliceosome) that cuts out segments of the messenger RNA (mRNA) and sticks the remaining parts back together. Scientists call this process “splicing”. Because mRNA molecules carry genetic information from chromosomes to cellular protein factories (ribosomes) where it is translated into proteins, splicing the mRNA can significantly change a cell's protein composition. Mishra and colleagues have now discovered that the binding of Hub1 to Snu66 decisively changes the properties of the spliceosome: With Hub1, it can also act on mRNAs that are normally not tailored. In some cases, spliceosomes modified by Hub1 can even generate two different mRNAs from just one gene. So-called “alternative splicing” provides the information for two different proteins from just one gene.

The Hub1-mediated mechanism that Jentsch and his co-workers discovered could be the oldest evolved mechanism that produces more proteins than there are genes. The researchers also found that it occurs in a preserved form from unicellular organisms such as yeast to humans. Since the mechanism presumably also has a significant influence on the production of human proteins, it will be of great relevance to both healthy and diseased human cells.