The smallest known open reading frame encodes the ribosomal protein L41, wh
ich in yeast is composed of only 24 amino acids, 17 of which are arginine o
r 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 t
o 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. T
he mRNAs are translated exclusively on monosomes, suggesting that ribosomes
do not remain attached to the mRNA after termination of translation. Calcu
lations based on the abundance of ribosomes and of L41 mRNA indicate that t
he entire translation event, from initiation through termination, must occu
r in similar to2 s. Termination of translation after only 25 codons does no
t 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.