Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts
In the post-genomic era, our understanding of the molecular regulators of physiologic and pathologic processes in pregnancy is expanding at the whole-genome level. Longitudinal changes in the known protein-coding transcriptome during normal pregnancy, which we recently reported (Gomez-Lopez et al.,...
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oai:doaj.org-article:0defabfcefd3498686dad1096cde59bf2021-11-22T06:41:03ZGestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts1664-802110.3389/fgene.2021.760849https://doaj.org/article/0defabfcefd3498686dad1096cde59bf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.760849/fullhttps://doaj.org/toc/1664-8021In the post-genomic era, our understanding of the molecular regulators of physiologic and pathologic processes in pregnancy is expanding at the whole-genome level. Longitudinal changes in the known protein-coding transcriptome during normal pregnancy, which we recently reported (Gomez-Lopez et al., 2019), have improved our definition of the major operant networks, yet pregnancy-related functions of the non-coding RNA transcriptome remain poorly understood. A key finding of the ENCODE (Encyclopedia of DNA Elements) Consortium, the successor of the Human Genome Project, was that the human genome contains approximately 60,000 genes, the majority of which do not encode proteins. The total transcriptional output of non-protein-coding RNA genes, collectively referred to as the non-coding transcriptome, is comprised mainly of long non-coding RNA (lncRNA) transcripts (Derrien et al., 2012). Although the ncRNA transcriptome eclipses its protein-coding counterpart in abundance, it has until recently lacked a comprehensive, unbiased, genome-scale characterization over the timecourse of normal human pregnancy. Here, we annotated, characterized, and selectively validated the longitudinal changes in the non-coding transcriptome of maternal whole blood during normal pregnancy to term. We identified nine long non-coding RNAs (lncRNAs), including long intergenic non-coding RNAs (lincRNAs) as well as lncRNAs antisense to or otherwise in the immediate vicinity of protein-coding genes, that were differentially expressed with advancing gestation in normal pregnancy: AL355711, BC039551 (expressed mainly in the placenta), JHDM1D-AS1, A2M-AS1, MANEA-AS1, NR_034004, LINC00649, LINC00861, and LINC01094. By cross-referencing our dataset against major public pseudogene catalogs, we also identified six transcribed pseudogenes that were differentially expressed over time during normal pregnancy in maternal blood: UBBP4, FOXO3B, two Makorin (MKRN) pseudogenes (MKRN9P and LOC441455), PSME2P2, and YBX3P1. We also identified three non-coding RNAs belonging to other classes that were modulated during gestation: the microRNA MIR4439, the small nucleolar RNA (snoRNA) SNORD41, and the small Cajal-body specific ncRNA SCARNA2. The expression profiles of most hits were broadly suggestive of functions in pregnancy. These time-dependent changes of the non-coding transcriptome during normal pregnancy, which may confer specific regulatory impacts on their protein-coding gene targets, will facilitate a deeper molecular understanding of pregnancy and lncRNA-mediated molecular pathways at the maternal-fetal interface and of how these pathways impact maternal and fetal health.Erica L. KleinbrinkNardhy Gomez-LopezNardhy Gomez-LopezNardhy Gomez-LopezDonghong JuBogdan DoneAnton-Scott GoustinAdi L. TarcaAdi L. TarcaAdi L. TarcaRoberto RomeroRoberto RomeroRoberto RomeroRoberto RomeroRoberto RomeroLeonard LipovichFrontiers Media S.A.articlefetal developmentRNA signaturegene networkscirculating lncRNAgestational ageGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
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| topic |
fetal development RNA signature gene networks circulating lncRNA gestational age Genetics QH426-470 |
| spellingShingle |
fetal development RNA signature gene networks circulating lncRNA gestational age Genetics QH426-470 Erica L. Kleinbrink Nardhy Gomez-Lopez Nardhy Gomez-Lopez Nardhy Gomez-Lopez Donghong Ju Bogdan Done Anton-Scott Goustin Adi L. Tarca Adi L. Tarca Adi L. Tarca Roberto Romero Roberto Romero Roberto Romero Roberto Romero Roberto Romero Leonard Lipovich Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| description |
In the post-genomic era, our understanding of the molecular regulators of physiologic and pathologic processes in pregnancy is expanding at the whole-genome level. Longitudinal changes in the known protein-coding transcriptome during normal pregnancy, which we recently reported (Gomez-Lopez et al., 2019), have improved our definition of the major operant networks, yet pregnancy-related functions of the non-coding RNA transcriptome remain poorly understood. A key finding of the ENCODE (Encyclopedia of DNA Elements) Consortium, the successor of the Human Genome Project, was that the human genome contains approximately 60,000 genes, the majority of which do not encode proteins. The total transcriptional output of non-protein-coding RNA genes, collectively referred to as the non-coding transcriptome, is comprised mainly of long non-coding RNA (lncRNA) transcripts (Derrien et al., 2012). Although the ncRNA transcriptome eclipses its protein-coding counterpart in abundance, it has until recently lacked a comprehensive, unbiased, genome-scale characterization over the timecourse of normal human pregnancy. Here, we annotated, characterized, and selectively validated the longitudinal changes in the non-coding transcriptome of maternal whole blood during normal pregnancy to term. We identified nine long non-coding RNAs (lncRNAs), including long intergenic non-coding RNAs (lincRNAs) as well as lncRNAs antisense to or otherwise in the immediate vicinity of protein-coding genes, that were differentially expressed with advancing gestation in normal pregnancy: AL355711, BC039551 (expressed mainly in the placenta), JHDM1D-AS1, A2M-AS1, MANEA-AS1, NR_034004, LINC00649, LINC00861, and LINC01094. By cross-referencing our dataset against major public pseudogene catalogs, we also identified six transcribed pseudogenes that were differentially expressed over time during normal pregnancy in maternal blood: UBBP4, FOXO3B, two Makorin (MKRN) pseudogenes (MKRN9P and LOC441455), PSME2P2, and YBX3P1. We also identified three non-coding RNAs belonging to other classes that were modulated during gestation: the microRNA MIR4439, the small nucleolar RNA (snoRNA) SNORD41, and the small Cajal-body specific ncRNA SCARNA2. The expression profiles of most hits were broadly suggestive of functions in pregnancy. These time-dependent changes of the non-coding transcriptome during normal pregnancy, which may confer specific regulatory impacts on their protein-coding gene targets, will facilitate a deeper molecular understanding of pregnancy and lncRNA-mediated molecular pathways at the maternal-fetal interface and of how these pathways impact maternal and fetal health. |
| format |
article |
| author |
Erica L. Kleinbrink Nardhy Gomez-Lopez Nardhy Gomez-Lopez Nardhy Gomez-Lopez Donghong Ju Bogdan Done Anton-Scott Goustin Adi L. Tarca Adi L. Tarca Adi L. Tarca Roberto Romero Roberto Romero Roberto Romero Roberto Romero Roberto Romero Leonard Lipovich |
| author_facet |
Erica L. Kleinbrink Nardhy Gomez-Lopez Nardhy Gomez-Lopez Nardhy Gomez-Lopez Donghong Ju Bogdan Done Anton-Scott Goustin Adi L. Tarca Adi L. Tarca Adi L. Tarca Roberto Romero Roberto Romero Roberto Romero Roberto Romero Roberto Romero Leonard Lipovich |
| author_sort |
Erica L. Kleinbrink |
| title |
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| title_short |
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| title_full |
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| title_fullStr |
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| title_full_unstemmed |
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts |
| title_sort |
gestational age dependence of the maternal circulating long non-coding rna transcriptome during normal pregnancy highlights antisense and pseudogene transcripts |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/0defabfcefd3498686dad1096cde59bf |
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