Structural Biology: Molecular Scissors Caught in the Act
Published:18 Sep.2023 Source:Goethe University Frankfurt
Transfer RNAs (tRNAs) are among the most common types of RNA in a cell and are indispensable for protein production in all known organisms. Transfer RNAs are generated from precursor tRNAs (pre-tRNAs), which are converted in several steps into the mature tRNA with a complex three-dimensional structure. In some tRNAs, this includes a step in which a certain section, known as an intron, is excised
The enzyme RNA kinase CLP1, which binds directly to TSEN, also plays a role in ensuring the correct conversion of tRNAs. If TSEN and CLP1 are unable to interact with each other due to a genetic mutation, it seems that tRNAs can no longer form correctly either. Although TSEN activity is essential for life, it was to date mostly unclear how the enzyme binds pre-tRNAs and how introns are excised. By means of cryo-electron microscopy (cryo-EM), researchers have now succeeded in shedding light on the three-dimensional structure of a TSEN/pre-tRNA complex.
With the aid of their cryo-EM reconstructions, the research team was able to show for the first time how TSEN interacts with the L-shaped pre-tRNA. TSEN then excises the intron from the long arm of the L. "First, TSEN settles in the corner of the L. It can then recognize both the short and the long arm as well as the angle between them," explains Trowitzsch. The subunit serves as a "molecular ruler" and measures the distance between the long and the short arm of the L. In this way, TSEN recognizes at which point the pre-tRNA needs to be cleaved in order to remove the intron.