RNA Controls Splicing: Implications for Origin of Life on Earth

RNA is a crucial part of life and now, scientists have discovered a little bit more about its importance. It turns out that RNA is the key functional component of spliceosomes, molecular machines that control how genes are expressed. The finding establishes that RNA and not protein is responsible for catalyzing this fundamental biological process. Not only that, it points to the hypothesis that life on Earth began in a world based solely on RNA.

For genes to be expressed, DNA must be translated into proteins, the structural and functional molecules that catalyze chemical reactions necessary for life. In order to do so, genetic information stored in DNA is first copied into strands of messenger RNA (mRNA) which are then used to create proteins.

In eukaryotes, almost all genes undergo alternative slicing. This process involves a prescursor form of mRNA being cut and re-stitched together in numerous different combinations. This increases the number of proteins a single gene codes for and could explain much of the complexity in higher-order organisms.

Spliceosomes, made from proteins and short, noncoding RNA fragments, actually carry out splicing via catalysts. However, previous research has hinted that RNA in the spliceosome might be responsible. In order to find out whether or not this is true, though, researchers decided to investigate a bit further.

The scientists first disabled the ability of spliceosomes to self-correct errors in splicing. They then modified single atoms at sites on mRNA precursors known to be cut during splicing, as well as several on U6, an RNA subunit of the spliceosome hypothesized to be important for catalysis. Some of these modifications rendered splicing to be ineffective. After systematically rescuing this loss-of function, the researchers were able to hone in on locations critical to splicing function.

In the end, the scientists found that the U6 RNA subunit directly controls catalytic function. It effectively acts as the blade of the spliceosome. This particular finding is the first experimental proof that RNA is the key functional component of this critical biological mechanism.

"In modern life, protein enzymes catalyze most biological reactions," said Joseph Piccirilli, one of the researchers, in a news release. "The finding that a system like the spliceosome, which contains more protein than RNA, uses RNA for catalysis and has a molecular ancestor composed entirely of RNA suggests that the spliceosome's reaction center may be a molecular fossil from the 'RNA World.'"

The findings are published in the journal Nature.