scholarly journals Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1491
Author(s):  
Silke Jensen ◽  
Emilie Brasset ◽  
Elise Parey ◽  
Hugues Roest Crollius ◽  
Igor V. Sharakhov ◽  
...  
Keyword(s):  
Regulatory Pathway ◽  
Cellular Functions ◽  
Germline Development ◽  
Protein Coding ◽  
Ping Pong ◽  
Sequence Complementarity ◽  
New Type ◽  
Non Coding Rnas ◽  
Pirna Pathway ◽  
Genomic Repeats

PIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In the Anopheles gambiae ovary, as much as 11% of piRNAs map to protein-coding genes. Here, we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short ~40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway.

scholarly journals Conserved small nucleotidic elements at the origin of concerted piRNA biogenesis from genes and lncRNAs

2020 ◽  
Author(s):  
Silke Jensen ◽  
Emilie Brasset ◽  
Elise Parey ◽  
Hugues Roest-Crollius ◽  
Igor V. Sharakhov ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Germ Cells ◽  
Germline Development ◽  
Protein Coding ◽  
Rna Molecules ◽  
Genetic Elements ◽  
Protein Coding Genes ◽  
Ping Pong ◽  
Sequence Complementarity ◽  
Non Coding Rnas

ABSTRACTPIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In the Anopheles gambiae ovary, as much as 11% of piRNAs map to protein-coding genes. Here we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short ∼40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of a conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway.AUTHOR SUMMARYSmall RNA molecules are essential actors in silencing mobile genetic elements in animal germ cells. The 24-29-nucleotide-long Piwi-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing. Mosquitoes of the Anopheles gambiae species complex are the principal vectors of malaria, and research on their germline is essential to develop new strategies of vector control by acting on reproduction. In the Anopheles gambiae ovary as much as 11% of piRNAs originate from protein-coding genes. We identified piRNAs which are able to target transcripts from several distinct genes or long non-coding RNAs (lncRNAs), bringing together genic transcripts and lncRNAs in a same regulation network. piRNA targeting induces transcript slicing and production of novel piRNAs, which then target other mRNAs and lncRNAs leading again to piRNA processing, thus resulting in a cascade of RNA slicing and piRNA production. Each network relies on piRNAs originating from repeated genetic elements, present in all transcripts of the same network. Some of these repeats are very short, only ∼40-nucleotides long. We identified similar repeats in all 43 animal species that we analysed, including mosquitoes, flies, arachnidae, snail, mouse, rat and human, suggesting that such regulation networks are recurrent, possibly conserved, in evolutionary history.

scholarly journals Functional profiling of long intergenic non-coding RNAs in fission yeast

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Maria Rodriguez-Lopez ◽  
Shajahan Anver ◽  
Cristina Cotobal ◽  
Stephan Kamrad ◽  
Michal Malecki ◽  
...  
Keyword(s):  
High Throughput ◽  
Cell Cycle Control ◽  
Colony Growth ◽  
Cellular Functions ◽  
Protein Coding ◽  
Functional Profiling ◽  
Functional Inference ◽  
Functional Context ◽  
Non Coding Rnas ◽  
Eukaryotic Genomes

Eukaryotic genomes express numerous long intergenic non-coding RNAs (lincRNAs) that do not overlap any coding genes. Some lincRNAs function in various aspects of gene regulation, but it is not clear in general to what extent lincRNAs contribute to the information flow from genotype to phenotype. To explore this question, we systematically analysed cellular roles of lincRNAs in Schizosaccharomyces pombe. Using seamless CRISPR/Cas9-based genome editing, we deleted 141 lincRNA genes to broadly phenotype these mutants, together with 238 diverse coding-gene mutants for functional context. We applied high-throughput colony-based assays to determine mutant growth and viability in benign conditions and in response to 145 different nutrient, drug, and stress conditions. These analyses uncovered phenotypes for 47.5% of the lincRNAs and 96% of the protein-coding genes. For 110 lincRNA mutants, we also performed high-throughput microscopy and flow cytometry assays, linking 37% of these lincRNAs with cell-size and/or cell-cycle control. With all assays combined, we detected phenotypes for 84 (59.6%) of all lincRNA deletion mutants tested. For complementary functional inference, we analysed colony growth of strains ectopically overexpressing 113 lincRNA genes under 47 different conditions. Of these overexpression strains, 102 (90.3%) showed altered growth under certain conditions. Clustering analyses provided further functional clues and relationships for some of the lincRNAs. These rich phenomics datasets associate lincRNA mutants with hundreds of phenotypes, indicating that most of the lincRNAs analysed exert cellular functions in specific environmental or physiological contexts. This study provides groundwork to further dissect the roles of these lincRNAs in the relevant conditions.

scholarly journals The Role of LncRNAs in Translation

2021 ◽  
Vol 7 (1) ◽  
pp. 16
Author(s):  
Didem Karakas ◽  
Bulent Ozpolat
Keyword(s):  
Transcriptional Activation ◽  
Chromatin Modification ◽  
Protein Translation ◽  
Cellular Functions ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Translational Machinery ◽  
Wide Range ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.

Non-coding RNAs: the cancer genome dark matter that matters!

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Hui Ling ◽  
Leonard Girnita ◽  
Octavian Buda ◽  
George A. Calin
Keyword(s):  
Cancer Biology ◽  
Drug Targets ◽  
Cancer Genome ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Sequence Complementarity ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
The Many ◽  
Carcinoma Renal Cell

AbstractProtein-coding genes comprise only 3% of the human genome, while the genes that are transcribed into RNAs but do not code for proteins occupy majority of the genome. Once considered as biological darker matter, non-coding RNAs are now being recognized as critical regulators in cancer genome. Among the many types of non-coding RNAs, microRNAs approximately 20 nucleotides in length are best characterized and their mechanisms of action are well generalized. microRNA exerts oncogenic or tumor suppressor function by regulation of protein-coding genes via sequence complementarity. The expression of microRNA is aberrantly regulated in all cancer types, and both academia and biotech companies have been keenly pursuing the potential of microRNA as cancer biomarker for early detection, prognosis, and therapeutic response. The key involvement of microRNAs in cancer also prompted interest on exploration of therapeutic values of microRNAs as anticancer drugs and drug targets. MRX34, a liposome-formulated miRNA-34 mimic, developed by Mirna Therapeutics, becomes the first microRNA therapeutic entering clinical trial for the treatment of hepatocellular carcinoma, renal cell carcinoma, and melanoma. In this review, we presented a general overview of microRNAs in cancer biology, the potential of microRNAs as cancer biomarkers and therapeutic targets, and associated challenges.

scholarly journals Role of Pseudogenes in Tumorigenesis

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 256 ◽  
Author(s):  
Xinling Hu ◽  
Liu Yang ◽  
Yin-Yuan Mo
Keyword(s):  
Critical Role ◽  
Cellular Functions ◽  
Protein Coding ◽  
Master Regulators ◽  
Protein Coding Genes ◽  
The Past ◽  
High Sequence Homology ◽  
Regulation Mechanisms ◽  
Non Coding Rnas

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

scholarly journals Integrated analysis of long non-coding RNAs and mRNAs reveals the regulatory network of maize seedling root responding to salt stress

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Peng Liu ◽  
Yinchao Zhang ◽  
Chaoying Zou ◽  
Cong Yang ◽  
Guangtang Pan ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Inbred Lines ◽  
Maize Seedling ◽  
Integrated Analysis ◽  
Regulatory Pathway ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rnas ◽  
Whole Transcriptome

Abstract Background Long non-coding RNAs (lncRNAs) play important roles in response to abiotic stresses in plants, by acting as cis- or trans-acting regulators of protein-coding genes. As a widely cultivated crop worldwide, maize is sensitive to salt stress particularly at the seedling stage. However, it is unclear how the expressions of protein-coding genes are affected by non-coding RNAs in maize responding to salt tolerance. Results The whole transcriptome sequencing was employed to investigate the differential lncRNAs and target transcripts responding to salt stress between two maize inbred lines with contrasting salt tolerance. We developed a flexible, user-friendly, and modular RNA analysis workflow, which facilitated the identification of lncRNAs and novel mRNAs from whole transcriptome data. Using the workflow, 12,817 lncRNAs and 8,320 novel mRNAs in maize seedling roots were identified and characterized. A total of 742 lncRNAs and 7,835 mRNAs were identified as salt stress-responsive transcripts. Moreover, we obtained 41 cis- and 81 trans-target mRNA for 88 of the lncRNAs. Among these target transcripts, 11 belonged to 7 transcription factor (TF) families including bHLH, C2H2, Hap3/NF-YB, HAS, MYB, WD40, and WRKY. The above 8,577 salt stress-responsive transcripts were further classified into 28 modules by weighted gene co-expression network analysis. In the salt-tolerant module, we constructed an interaction network containing 79 nodes and 3081 edges, which included 5 lncRNAs, 18 TFs and 56 functional transcripts (FTs). As a trans-acting regulator, the lncRNA MSTRG.8888.1 affected the expressions of some salt tolerance-relative FTs, including protein-serine/threonine phosphatase 2C and galactinol synthase 1, by regulating the expression of the bHLH TF. Conclusions The contrasting genetic backgrounds of the two inbred lines generated considerable variations in the expression abundance of lncRNAs and protein-coding transcripts. In the co-expression networks responding to salt stress, some TFs were targeted by the lncRNAs, which further regulated the salt tolerance-related functional transcripts. We constructed a regulatory pathway of maize seedlings to salt stress, which was mediated by the hub lncRNA MSTRG.8888.1 and participated by the bHLH TF and its downstream target transcripts. Future work will be focused on the functional revelation of the regulatory pathway.

scholarly journals The expanding regulatory universe of p53 in gastrointestinal cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 756 ◽  
Author(s):  
Andrew Fesler ◽  
Ning Zhang ◽  
Jingfang Ju
Keyword(s):  
Gastrointestinal Cancer ◽  
Regulatory Network ◽  
Cancer Biology ◽  
Control Cell ◽  
Cellular Functions ◽  
Protein Coding ◽  
Growth Environment ◽  
Damage Repair ◽  
Non Coding Rnas ◽  
And Function

Tumor suppresser geneTP53is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

The piRNA pathway in planarian flatworms: new model, new insights

2020 ◽  
Vol 401 (10) ◽  
pp. 1123-1141
Author(s):  
Iana V. Kim ◽  
Sebastian Riedelbauch ◽  
Claus-D. Kuhn
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Adult Stem Cells ◽  
Germline Development ◽  
Molecular Feature ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Small Regulatory Rnas ◽  
Stable Genome ◽  
Pirna Pathway

AbstractPIWI-interacting RNAs (piRNAs) are small regulatory RNAs that associate with members of the PIWI clade of the Argonaute superfamily of proteins. piRNAs are predominantly found in animal gonads. There they silence transposable elements (TEs), regulate gene expression and participate in DNA methylation, thus orchestrating proper germline development. Furthermore, PIWI proteins are also indispensable for the maintenance and differentiation capabilities of pluripotent stem cells in free-living invertebrate species with regenerative potential. Thus, PIWI proteins and piRNAs seem to constitute an essential molecular feature of somatic pluripotent stem cells and the germline. In keeping with this hypothesis, both PIWI proteins and piRNAs are enriched in neoblasts, the adult stem cells of planarian flatworms, and their presence is a prerequisite for the proper regeneration and perpetual tissue homeostasis of these animals. The piRNA pathway is required to maintain the unique biology of planarians because, in analogy to the animal germline, planarian piRNAs silence TEs and ensure stable genome inheritance. Moreover, planarian piRNAs also contribute to the degradation of numerous protein-coding transcripts, a function that may be critical for neoblast differentiation. This review gives an overview of the planarian piRNA pathway and of its crucial function in neoblast biology.

scholarly journals Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu H. Sun ◽  
Ruoqiao Huiyi Wang ◽  
Khai Du ◽  
Jiang Zhu ◽  
Jihong Zheng ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Transposable Element ◽  
Small Rnas ◽  
Protein Production ◽  
Fine Tuning ◽  
Untranslated Regions ◽  
Protein Coding ◽  
Rna Surveillance ◽  
Non Coding Rnas ◽  
Pirna Pathway

AbstractPIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. piRNAs originate from transposable element (TE) RNAs, long non-coding RNAs, or 3´ untranslated regions (3´UTRs) of protein-coding messenger genes, with the last being the least characterized of the three piRNA classes. Here, we demonstrate that the precursors of 3´UTR piRNAs are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3´UTRs in mice and chickens. At the pachytene stage, when other co-translational RNA surveillance pathways are sequestered, piRNA biogenesis degrades mRNAs right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Although 3´UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded TEs and produce piRNAs that cleave TEs. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved piRNA biogenesis mechanism that recognizes translating RNAs in amniotes.

piRNA-Guided Genome Defense: From Biogenesis to Silencing

2018 ◽  
Vol 52 (1) ◽  
pp. 131-157 ◽  
Author(s):  
Benjamin Czech ◽  
Marzia Munafò ◽  
Filippo Ciabrelli ◽  
Evelyn L. Eastwood ◽  
Martin H. Fabry ◽  
...  
Keyword(s):  
Transcriptional Gene Silencing ◽  
Cytoplasmic Process ◽  
Main Function ◽  
Argonaute Proteins ◽  
Repressive Chromatin ◽  
Genome Defense ◽  
Ping Pong ◽  
Sequence Complementarity ◽  
And Function ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) and their associated PIWI clade Argonaute proteins constitute the core of the piRNA pathway. In gonadal cells, this conserved pathway is crucial for genome defense, and its main function is to silence transposable elements. This is achieved through posttranscriptional and transcriptional gene silencing. Precursors that give rise to piRNAs require specialized transcription and transport machineries because piRNA biogenesis is a cytoplasmic process. The ping-pong cycle, a posttranscriptional silencing mechanism, combines the cleavage-dependent silencing of transposon RNAs with piRNA production. PIWI proteins also function in the nucleus, where they scan for nascent target transcripts with sequence complementarity, instructing transcriptional silencing and deposition of repressive chromatin marks at transposon loci. Although studies have revealed numerous factors that participate in each branch of the piRNA pathway, the precise molecular roles of these factors often remain unclear. In this review, we summarize our current understanding of the mechanisms involved in piRNA biogenesis and function.

Sign in / Sign up

Export Citation Format

Share Document