Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium

Lluch-Senar, Maria 1982-; Delgado Blanco, Javier; Chen, Wei-Hua; Lloréns Rico, Verónica, 1989-; O’Reilly, Francis J.; Wodke, Judith A.H.; Unal, E. Besray; Yus, Eva; Martínez, Sira; Nichols, Robert J.; Ferrar, Tony; Vivancos Prellezo, Ana; Schmeisky, Arne; Stülke, Jörg; Noort, Vera van; Gavin, Anne-Claude; Bork, Peer; Serrano Pubull, Luis, 1982-

doi:http://dx.doi.org/10.15252/msb.20145558

Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium

Citation

Lluch-Senar M, Delgado J, Chen WH, Lloréns-Rico V, O'Reilly FJ, Wodke JA et al. Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium. Molecular systems biology. 2015;11(1):780. DOI: 10.15252/msb.20145558

Abstract

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.