title: Integrative classification of human coding and noncoding genes through RNA metabolism profiles.
abstract: Pervasive transcription of the human genome results in a heterogeneous mix of coding RNAs and long noncoding RNAs (lncRNAs). Only a small fraction of lncRNAs have demonstrated regulatory functions, thus making functional lncRNAs difficult to distinguish from nonfunctional transcriptional byproducts. This difficulty has resulted in numerous competing human lncRNA classifications that are complicated by a steady increase in the number of annotated lncRNAs. To address these challenges, we quantitatively examined transcription, splicing, degradation, localization and translation for coding and noncoding human genes. We observed that annotated lncRNAs had lower synthesis and higher degradation rates than mRNAs and discovered mechanistic differences explaining slower lncRNA splicing. We grouped genes into classes with similar RNA metabolism profiles, containing both mRNAs and lncRNAs to varying extents. These classes exhibited distinct RNA metabolism, different evolutionary patterns and differential sensitivity to cellular RNA-regulatory pathways. Our classification provides an alternative to genomic context-driven annotations of lncRNAs.
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Biology, Humboldt University, Berlin, Germany.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Calviello
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Hirsekorn
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Instituto Italiano di Tecnologia, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: de Pretis
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Instituto Italiano di Tecnologia, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Pelizzola
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Biology, Humboldt University, Berlin, Germany.|Department of Computer Science, Humboldt University, Berlin, Germany.
authors.forename: Uwe
authors.identifier: 0000-0002-0881-3116
authors.initials: U
authors.lastname: Ohler
mesh_terms: D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D058977:Molecular Sequence Annotation; D016366:Open Reading Frames; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated