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Scientists from the University of Chicago have deciphered the catalytic core of spliceosomes, providing a strong argument for the RNA world hypothesis, which claims that earlier forms of life may have relied solely on RNA to store genetic information and to catalyze chemical reactions.

Spliceosomes are part of the molecular machinery of the cell, located in the nucleus of eukaryotes, and responsible for processing of precursor mRNA (pre-mRNA) molecules. By removal of introns, spliceosomes produce functional mRNA molecules, which can travel to ribosomes and participate in protein synthesis.

Spliceosome is known to be composed of small nuclear RNAs (snRNAs) and proteins, but which of these structural parts catalyze splicing of pre-mRNA has been unclear. It has been postulated, however, that spliceosome is, in fact, a ribozyme and its activity is based on RNA, not proteins.

Self-splicing RNAs is a known phenomenon is molecular science. Moreover, snRNAs have been found to share functional and structural similarities with self-catalytic ribozymes found in rRNA, tRNA and mRNA of eukaryotes, and mRNA of prokaryotes. In fact, two particular snRNAs found within spliceosomes have been observed to fold into a structure similar to that involved in several steps of pre-mRNA splicing.

A study published in Nature looked at the catalytic core of spliceosomes, which comes in contact with the splice sites of pre-mRNA by two catalytic metals. The involvement of metals in the initiation of splicing has been established before; however, which molecules – snRNAs or proteins – directly bind these metals, and, therefore, are directly involved in splicing, has been up for discussion until now.

By pin-pointing the metal binding sites in a fully assembled spliceosome, the researchers were able to show the phosphate backbones of particular snRNAs are, in fact, a perfect match, allowing them to participate in the catalytic steps of splicing. These results are also consistent with the common evolutionary origins of snRNAs and self-splicing RNAs.

As the evidence suggests, RNAs can carry out the essential role of splicing without any involvement of proteins. Similarly to the function of the ribosome, this once again proves that RNAs can be the main catalytic units within RNA-protein complexes, carrying out essential cell functions. This tips the scales in favor of the RNA, in the ever-lasting clash of replicator-first and metabolism-first hypotheses.

Source: www.technology.org