Abstract
Over the past decade, there has been an increase in the appreciation of the role of non-coding RNA in the development of organism phenotype. It is possible to divide the non-coding elements of the transcriptome into three categories: short non-coding RNAs, circular RNAs and long non-coding RNAs. Long non-coding RNAs are those transcripts that are greater than 200 nts in length and lack any significant open reading frames that produce proteins greater then 100 amino acids. Long intervening non-coding RNAs (lincRNAs) are a subclass of long non-coding RNAs. In contrast to protein coding RNAs, lincRNAs are expressed in a more tissue- and species-specific manner. In particular, many lincRNAs are only conserved amongst higher primates. This coupled with the propensity of many lincRNAs to be expressed in the brain, suggests that they are in fact one of the major drivers of organism complexity. We analysed 39 lincRNAs that are expressed in the frontal cortex and identified LINC00507 as being expressed in a cortex-specific manner in non-human primates and humans. The expression patterns of LINC00507 appear to be age-dependent, suggesting it may be involved in brain development of higher primates. Moreover, the analysis of LINC00507 potential to bind ribosomes revealed that this previously identified non-coding transcript may harbour a micropeptide.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160:595–606
Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927
Darmanis S, Sloan SA, Zhang Y, Enge M, Caneda C, Shuer LM, Hayden Gephart MG, Barres BA, Quake SR (2015) A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci U S A 112:7285–7290
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789
Fu X, Giavalisco P, Liu X, Catchpole G, Fu N, Ning ZB, Guo S, Yan Z, Somel M, Paabo S, Zeng R, Willmitzer L, Khaitovich P (2011) Rapid metabolic evolution in human prefrontal cortex. Proc Natl Acad Sci U S A 108:6181–6186
Galindo MI, Pueyo JI, Fouix S, Bishop SA, Couso JP (2007) Peptides encoded by short ORFs control development and define a new eukaryotic gene family. PLoS Biol 5:e106
Gonzalez C, Sims JS, Hornstein N, Mela A, Garcia F, Lei L, Gass DA, Amendolara B, Bruce JN, Canoll P, Sims PA (2014) Ribosome profiling reveals a cell-type-specific translational landscape in brain tumors. J Neurosci 34:10924–10936
Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477:295–300
Hashimoto Y, Kondo T, Kageyama Y (2008) Lilliputians get into the limelight: novel class of small peptide genes in morphogenesis. Develop Growth Differ 50(Suppl 1):S269–S276
Haygood R, Babbitt CC, Fedrigo O, Wray GA (2010) Contrasts between adaptive coding and noncoding changes during human evolution. Proc Natl Acad Sci U S A 107:7853–7857
He Z, Bammann H, Han D, Xie G, Khaitovich P (2014) Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation. Rna 20:1103–1111
Hezroni H, Koppstein D, Schwartz MG, Avrutin A, Bartel DP, Ulitsky I (2015) Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep 11:1110–1122
Huttenlocher PR, Dabholkar AS (1997) Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387:167–178
Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:218–223
Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672
Kutter C, Watt S, Stefflova K, Wilson MD, Goncalves A, Ponting CP, Odom DT, Marques AC (2012) Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet 8:e1002841
Mattick JS, Rinn JL (2015) Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 22:5–7
Mele M, PG F, Reverter F, DS DL, Monlong J, Sammeth M, TR Y, JM G, DD P, TJ S, Johnson R, AV S, Djebali S, Niarchou A, GT C, FA W, Lappalainen T, Calvo M, Getz G, ET D, KG A, Guigo R (2015) Human genomics. The human transcriptome across tissues and individuals. Science 348:660–665
Mills JD, Kavanagh T, Kim WS, Chen BJ, Waters PD, Halliday GM, Janitz M (2015a) High expression of long intervening non-coding RNA OLMALINC in the human cortical white matter is associated with regulation of oligodendrocyte maturation. Mol Brain 8:2
Mills JD, Chen J, Kim WS, Waters PD, Prabowo AS, Aronica E, Halliday GM, Janitz M (2015b) Long intervening non-coding RNA 00320 is human brain-specific and highly expressed in the cortical white matter. Neurogenetics 16:201–213
Mills JD, Kavanagh T, Kim WS, Chen BJ, Kawahara Y, Halliday GM, Janitz M (2013) Unique transcriptome patterns of the white and grey matter corroborate structural and functional heterogeneity in the human frontal lobe. PLoS One 8:e78480
Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grutzner F, Kaessmann H (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505:635–640
Petanjek Z, Judas M, Simic G, Rasin MR, Uylings HB, Rakic P, Kostovic I (2011) Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc Natl Acad Sci U S A 108:13281–13286
Ramakers C, Ruijter JM, Deprez RHL, Moorman AF (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Let 339:62–66
Sauvageau M, Goff LA, Lodato S, Bonev B, Groff AF, Gerhardinger C, Sanchez-Gomez DB, Hacisuleyman E, Li E, Spence M, Liapis SC, Mallard W, Morse M, Swerdel MR, D'Ecclessis MF, Moore JC, Lai V, Gong G, Yancopoulos GD, Frendewey D, Kellis M, Hart RP, Valenzuela DM, Arlotta P, Rinn JL (2013) Multiple knockout mouse models reveal lincRNAs are required for life and brain development. Elife 2:e01749
Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA, Team MGCP (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A 99:16899–16903
Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562–578
Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–1550
Wan Y, Qu K, Zhang QC, Flynn RA, Manor O, Ouyang Z, Zhang J, Spitale RC, Snyder MP, Segal E, Chang HY (2014) Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505:706–709
Ward M, McEwan C, Mills JD, Janitz M (2015) Conservation and tissue-specific transcription patterns of long noncoding RNAs. J Hum Transcriptome 1:2–9
Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9:133–148
Acknowledgments
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171) and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 and DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 and MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina–Chapel Hill (MH090936 and MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822). This research was supported by the Framework Programme FP7/2007-2013 under the project EPISTOP (grant agreement no: 602391 to EA) and (NeuroGeM grant 733051052 to EA and JDM).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Electronic supplementary materials
Supplementary Figure 1
Tissue-specific expression patterns of LINC00507. Out of 53 different tissue types LINC00507 only appears to be expressed in the brain. More specifically, expression was only detected in the anterior cingulate cortex, cortex and frontal cortex. Only basal levels of expression were seen in other tissue types. Expression (y-axis) is in reads per kilobase of transcript per million mapped reads (RPKM). The figure was produced using the GTEx database. (PNG 98 kb)
Supplementary Figure 2
Splice variants of LINC00507. LINC00507 is alternatively spliced, producing three splice variants, LINC00507-001, LINC00507-002, LINC00507-003 (Ensembl IDs). Exons are indicated by open rectangles, introns are indicated by lines. Figure adapted from Ensembl (http://asia.ensembl.org/index.html). (PNG 17 kb)
ESM 1
(DOCX 16 kb)
Rights and permissions
About this article
Cite this article
Mills, J.D., Ward, M., Chen, B.J. et al. LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns. J Mol Neurosci 59, 431–439 (2016). https://doi.org/10.1007/s12031-016-0745-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-016-0745-4