scholarly journals Characterization of testis-specific LINC01016 gene reveals isoform-specific roles in controlling biological processes

2021 ◽  
Author(s):  
Enrique I Ramos ◽  
Barbara Yang ◽  
Yasmin M Vasquez ◽  
Ken Y Lin ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
De Novo ◽  
Biological Processes ◽  
Detailed Characterization ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Lncrna Gene ◽  
Gene Expression Analyses ◽  
Uterine Cancers ◽  
Exon Usage

Abstract Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. However, the aberrant expression of an isoform from the same lncRNA gene could lead to RNA with altered functions due to changes in their conformations, leading to diseases. Here, we describe a detailed characterization of the gene which encodes long intergenic non-protein coding RNA 01016 (LINC01016, a.k.a., LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study, we show that it is among the highly expressed lncRNAs in the testis, exclusively conserved among non-human primates, suggesting its recent evolution and is expressed and processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multi-exon gene, processed through differential exon usage with isoform-specific roles. Furthermore, in cervical, testicular, and uterine cancers, LINC01016 isoforms are differentially expressed, and their expression is predictive of survival in these cancers. The study has revealed an essential aspect of lncRNA biology, which is rarely associated with coding RNAs that lncRNA genes are precisely processed to generate isoforms with distinct biological roles in specific tissues.

scholarly journals Gene structure, differential exon usage, and expression of the testis long intergenic non-protein coding RNA 1016 in humans reveals isoform-specific roles in controlling biological processes

2021 ◽  
Author(s):  
Enrique I Ramos ◽  
Barbara Yang ◽  
Yasmin M Vasquez ◽  
Ken Y Lin ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
De Novo ◽  
Cervical Squamous Cell Carcinoma ◽  
Biological Processes ◽  
Relapse Free Survival ◽  
Detailed Characterization ◽  
Protein Coding ◽  
Free Survival ◽  
Gene Expression Analyses ◽  
Exon Usage

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. The constant expansion of newly-identified lncRNA genes requires that each one be comprehensively annotated to understand its molecular functions. Here, we describe a detailed characterization of the gene which encodes long intergenic non-protein coding RNA 01016 (LINC01016, a.k.a., LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study, we show that it is exclusively conserved among non-human primates, suggesting its recent evolution and is expressed and processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multi-exon gene, processed through differential exon usage with isoform-specific functions. Furthermore, in gynecological cancers, such as cervical squamous cell carcinoma and uterine corpus endometrial carcinoma, LINC01016 is downregulated; however, its higher expression is predictive of relapse-free survival in these cancers. Collectively, these analyses reveal that, unlike coding RNAs, lncRNA isoforms are differentially regulated and precisely processed in specific tissues to perform distinct biological roles.

scholarly journals Promising Advances in LINC01116 Related to Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Qingyuan Zheng ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Lung Cancer ◽  
Cancer Colorectal ◽  
Malignant Tumors ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Future Studies ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are RNAs with a length of no less than 200 nucleotides that are not translated into proteins. Accumulating evidence indicates that lncRNAs are pivotal regulators of biological processes in several diseases, particularly in several malignant tumors. Long intergenic non-protein coding RNA 1116 (LINC01116) is a lncRNA, whose aberrant expression is correlated with a variety of cancers, including lung cancer, gastric cancer, colorectal cancer, glioma, and osteosarcoma. LINC01116 plays a crucial role in facilitating cell proliferation, invasion, migration, and apoptosis. In addition, numerous studies have recently suggested that LINC01116 has emerged as a novel biomarker for prognosis and therapy in malignant tumors. Consequently, we summarize the clinical significance of LINC01116 associated with biological processes in various tumors and provide a hopeful orientation to guide clinical treatment of various cancers in future studies.

scholarly journals Long Non-Coding RNAs and Related Molecular Pathways in the Pathogenesis of Epilepsy

2019 ◽  
Vol 20 (19) ◽  
pp. 4898 ◽  
Author(s):  
Villa ◽  
Lavitrano ◽  
Combi
Keyword(s):  
Biological Processes ◽  
Complete Understanding ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Diagnostic Biomarkers ◽  
Functional Roles ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Coding Capacity

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets.

scholarly journals Fact or fiction: updates on how protein-coding genes might emerge de novo from previously non-coding DNA

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 57 ◽  
Author(s):  
Jonathan F Schmitz ◽  
Erich Bornberg-Bauer
Keyword(s):  
De Novo ◽  
Protein Structures ◽  
Divergence Times ◽  
Protein Coding ◽  
Future Studies ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Open Questions ◽  
Bona Fide

Over the last few years, there has been an increasing amount of evidence for the de novo emergence of protein-coding genes, i.e. out of non-coding DNA. Here, we review the current literature and summarize the state of the field. We focus specifically on open questions and challenges in the study of de novo protein-coding genes such as the identification and verification of de novo-emerged genes. The greatest obstacle to date is the lack of high-quality genomic data with very short divergence times which could help precisely pin down the location of origin of a de novo gene. We conclude that, while there is plenty of evidence from a genetics perspective, there is a lack of functional studies of bona fide de novo genes and almost no knowledge about protein structures and how they come about during the emergence of de novo protein-coding genes. We suggest that future studies should concentrate on the functional and structural characterization of de novo protein-coding genes as well as the detailed study of the emergence of functional de novo protein-coding genes.

scholarly journals A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression

2020 ◽  
Vol 295 (38) ◽  
pp. 13202-13212
Author(s):  
Lucas Pagura ◽  
Evelyn Tevere ◽  
Marcelo L. Merli ◽  
Julia A. Cricco
Keyword(s):  
Trypanosoma Cruzi ◽  
De Novo ◽  
Mrna Levels ◽  
Biological Processes ◽  
Transport Activity ◽  
Critical Pathway ◽  
Heme Transport ◽  
Life Cycle Stages ◽  
Insight Into

Heme is an essential cofactor for many biological processes in aerobic organisms, which can synthesize it de novo through a conserved pathway. Trypanosoma cruzi, the etiological agent of Chagas disease, as well as other trypanosomatids relevant to human health, are heme auxotrophs, meaning they must import it from their mammalian hosts or insect vectors. However, how these species import and regulate heme levels is not fully defined yet. It is known that the membrane protein TcHTE is involved in T. cruzi heme transport, although its specific role remains unclear. In the present work, we studied endogenous TcHTE in the different life cycle stages of the parasite to gain insight into its function in heme transport and homeostasis. We have confirmed that TcHTE is predominantly detected in replicative stages (epimastigote and amastigote), in which heme transport activity was previously validated. We also showed that in epimastigotes, TcHTE protein and mRNA levels decrease in response to increments in heme concentration, confirming it as a member of the heme response gene family. Finally, we demonstrated that T. cruzi epimastigotes can sense intracellular heme by an unknown mechanism and regulate heme transport to adapt to changing conditions. Based on these results, we propose a model in which T. cruzi senses intracellular heme and regulates heme transport activity by adjusting the expression of TcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of a critical pathway for T. cruzi biology allowing the identification of novel and essential proteins.

scholarly journals Structural and functional characterization of a putative de novo gene in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andreas Lange ◽  
Prajal H. Patel ◽  
Brennen Heames ◽  
Adam M. Damry ◽  
Thorsten Saenger ◽  
...  
Keyword(s):  
De Novo ◽  
Functional Characterization ◽  
Comparative Genomic ◽  
Noncoding Dna ◽  
Protein Coding ◽  
Ancestral Sequences ◽  
De Novo Gene ◽  
Genomic Studies ◽  
Biochemical Genetic

AbstractComparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from noncoding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus. Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and circular dichroism (CD) data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.

scholarly journals Transcriptomic and Epigenomic Landscape in Rett Syndrome

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 967
Author(s):  
Domenico Marano ◽  
Salvatore Fioriniello ◽  
Maurizio D'Esposito ◽  
Floriana Della Ragione
Keyword(s):  
Rett Syndrome ◽  
Transcriptional Activation ◽  
Large Scale ◽  
Developmental Disorder ◽  
De Novo ◽  
Current Knowledge ◽  
Biological Processes ◽  
De Novo Mutations ◽  
Protein Coding ◽  
Methylated Dna

Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2 is a master epigenetic modulator of gene expression, with a role in the organization of global chromatin architecture. Based on its interaction with multiple molecular partners and the diverse epigenetic scenario, MeCP2 triggers several downstream mechanisms, also influencing the epigenetic context, and thus leading to transcriptional activation or repression. In this frame, it is conceivable that defects in such a multifaceted factor as MeCP2 lead to large-scale alterations of the epigenome, ranging from an unbalanced deposition of epigenetic modifications to a transcriptional alteration of both protein-coding and non-coding genes, with critical consequences on multiple downstream biological processes. In this review, we provide an overview of the current knowledge concerning the transcriptomic and epigenomic alterations found in RTT patients and animal models.

scholarly journals Evolutionary Characterization of the Short Protein SPAAR

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1864
Author(s):  
Jiwon Lee ◽  
Aaron Wacholder ◽  
Anne-Ruxandra Carvunis
Keyword(s):  
Muscle Regeneration ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Sequence Divergence ◽  
Biological Processes ◽  
Noncoding Sequence ◽  
Homology Detection ◽  
Evolutionary Innovation ◽  
Short Protein

Microproteins (<100 amino acids) are receiving increasing recognition as important participants in numerous biological processes, but their evolutionary dynamics are poorly understood. SPAAR is a recently discovered microprotein that regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways. Interestingly, SPAAR does not belong to any known protein family and has known homologs exclusively among placental mammals. This lack of distant homology could be caused by challenges in homology detection of short sequences, or it could indicate a recent de novo emergence from a noncoding sequence. By integrating syntenic alignments and homology searches, we identify SPAAR orthologs in marsupials and monotremes, establishing that SPAAR has existed at least since the emergence of mammals. SPAAR shows substantial primary sequence divergence but retains a conserved protein structure. In primates, we infer two independent evolutionary events leading to the de novo origination of 5′ elongated isoforms of SPAAR from a noncoding sequence and find evidence of adaptive evolution in this extended region. Thus, SPAAR may be of ancient origin, but it appears to be experiencing continual evolutionary innovation in mammals.

scholarly journals Distribution of subtypes and immunophenotypic characterization of 1379 cases of paediatric acute leukaemia

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Saba Jamal ◽  
Fatima Meraj ◽  
Neelum Mansoor ◽  
Sadia Parveen ◽  
Ameerah Shaikh ◽  
...  
Keyword(s):  
Acute Leukaemia ◽  
De Novo ◽  
Residual Disease ◽  
Treatment Plan ◽  
Phenotypic Expression ◽  
University Hospital ◽  
Morphological Examination ◽  
Aberrant Expression ◽  
Female Ratio

Objectives: Acute leukaemia is the most common and highly curable childhood malignancy; subtyping and identification of antigens via immunophenotyping helps in treatment plan as well as minimal residual disease monitoring. Methods: This retrospective study was conducted at the Haematology section of the clinical laboratories of Ziauddin University Hospital and The Indus Hospital, Karachi conducted at January 1st, 2012 to December 31st, 2017. The study included 1379 cases of de novo acute leukemia from 2012 to 2017. Among these, 80% were diagnosed by using four color flowcytometry (FACS Calibur), 9% and 11% via immunohistochemistry on bone marrow trephine biopsy samples and morphological examination respectively. Results: The mean age of patients was 7.4 ± 4.3 years while male to female ratio was 1.75:1. Lymphoblastic leukaemia accounted for 77.2% and myeloid leukaemia 21.2%. Amongst lymphoblastic lineage, B-ALL was 80.4% while T-ALL was 19.6%. Among the phenotypic expression of B-ALL, CD79a (99.8%) had the highest positivity. In B-ALL, CD13 (29.8%) was the most common aberrant myeloid marker. Aberrant expression of CD79a observed in 11.1% of T-ALL cases. In non APL AML, aberrant expression of CD79a and CD19 was observed in 6.6% and 5.5% of cases respectively. Conclusion: Overall immunophenotypic profile, expression of aberrant phenotypes and subtype distribution in our patients was similar to international literature except for a relatively high frequency of T-ALL which was discordant from the western data. doi: https://doi.org/10.12669/pjms.37.3.3552 How to cite this:Jamal S, Meraj F, Mansoor N, Parveen S, Shaikh A, Jabbar N. Distribution of subtypes and immunophenotypic characterization of 1379 cases of paediatric acute leukaemia. Pak J Med Sci. 2021;37(3):---------.  doi: https://doi.org/10.12669/pjms.37.3.3552 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals PHASIS: A computational suite for de novo discovery and characterization of phased, siRNA-generating loci and their miRNA triggers

2017 ◽  
Author(s):  
Atul Kakrana ◽  
Pingchuan Li ◽  
Parth Patel ◽  
Reza Hammond ◽  
Deepti Anand ◽  
...  
Keyword(s):  
De Novo ◽  
Sequencing Data ◽  
Protein Coding ◽  
Secondary Sirnas ◽  
Integrated Methods ◽  
Non Coding Rnas

AbstractPhased, secondary siRNAs (phasiRNAs) are found widely in plants, from protein-coding transcripts and long, non-coding RNAs; animal piRNAs are also phased. Integrated methods characterizing “PHAS” loci are unavailable, and existing methods are quite limited and inefficient in handling large volumes of sequencing data. The PHASIS suite described here provides complete tools for the computational characterization of PHAS loci, with an emphasis on plants, in which these loci are numerous. Benchmarked comparisons demonstrate that PHASIS is sensitive, highly scalable and fast. Importantly, PHASIS eliminates the requirement of a sequenced genome and PARE/degradome data for discovery of phasiRNAs and their miRNA triggers.

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