Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium.
Lluch-Senar M, Delgado J, Chen WH
, Lloréns-Rico V, O'Reilly FJ, Wodke JA, Unal EB, Yus E, Martínez S, Nichols RJ, Ferrar T, Vivancos A, Schmeisky A, Stülke J, van Noort V
, Gavin AC, Bork P
, Serrano L
Mol Syst Biol.
2015 Jan 21; 11(1): 780. PubMed: 25609650.
Abstract + PDF
Identifying all essential genomic components is critical for the assembly of minimal artificial life. In the genome-reduced bacterium Mycoplasma pneumoniae, we found that small ORFs (smORFs; < 100 residues), accounting for 10% of all ORFs, are the most frequently essential genomic components (53%), followed by conventional ORFs (49%). Essentiality of smORFs may be explained by their function as members of protein and/or DNA/RNA complexes. In larger proteins, essentiality applied to individual domains and not entire proteins, a notion we could confirm by expression of truncated domains. The fraction of essential non-coding RNAs (ncRNAs) non-overlapping with essential genes is 5% higher than of non-transcribed regions (0.9%), pointing to the important functions of the former. We found that the minimal essential genome is comprised of 33% (269,410 bp) of the M. pneumoniae genome. Our data highlight an unexpected hidden layer of smORFs with essential functions, as well as non-coding regions, thus changing the focus when aiming to define the minimal essential genome.