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The smallest known open reading frame encodes the ribosomal protein L41, which in yeast is composed of only 24 amino acids, 17 of which are arginine or lysine. Because of the unique problems that might attend the translation of such a short open reading frame, we have investigated the properties and the translation of the mRNAs encoding L41. In Saccharomyces cerevisiae L41 is encoded by two linked genes, RPL41A and RPL41B. These genes give rise to mRNAs that have short 5' leaders of 18 and 22 nucleotides and rather long 3' leaders of 203 and 210 nucleotides not including their poly(A) tails. The mRNAs are translated exclusively on monosomes, suggesting that ribosomes do not remain attached to the mRNA after termination of translation. Calculations based on the abundance of ribosomes and of L41 mRNA indicate that the entire translation event, from initiation through termination, must occur in approximately 2 s. Termination of translation after only 25 codons does not subject the mRNAs encoding L41 to nonsense-mediated decay. Surprisingly, despite the L41 ribosomal protein being conserved from the archaea through the mammalia, S. cerevisiae can grow relatively normally after deletion of both RPL41A and RPL41B.


X Yu, J R Warner. Expression of a micro-protein. The Journal of biological chemistry. 2001 Sep 7;276(36):33821-5

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PMID: 11451953

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