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.

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

2021 ◽  
Author(s):  
Yu H. Sun ◽  
Ruoqiao Huiyi Wang ◽  
Khai Du ◽  
Jihong Zheng ◽  
Li Huitong Xie ◽  
...  
Keyword(s):  
Small Rnas ◽  
Protein Production ◽  
Open Reading Frames ◽  
Fine Tuning ◽  
Untranslated Regions ◽  
Protein Coding ◽  
Evolutionary Force ◽  
Non Coding Rnas ◽  
Pirna Pathway ◽  
Reading Frames

PIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. Previously, we showed that ribosomes guide the biogenesis of piRNAs from long non-coding RNAs (lncRNAs) after translating the short open reading frames (ORFs) near their 5' cap. It remained unclear, however, how ribosomes proceed downstream of ORFs and how piRNA precursors distinguish from other RNAs. It is thus important to test whether a short ORF length is required for substrate recognition for ribosome guided-piRNA biogenesis. Here, we characterized a poorly understood class of piRNAs that originate from the 3' untranslated regions (3'UTRs) of protein coding genes in mice and chickens. We demonstrate that their precursors are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3'UTRs after translation of upstream long ORFs. Similar to non-sense mediated decay (NMD), piRNA biogenesis degrades mRNA right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Interestingly, however, we found that NMD, along with other surveillance pathways for ribosome recycling are temporally sequestered during the pachytene stage to allow for robust piRNA production. Although 3'UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded transposable elements (TEs) and produce piRNAs that cleave TEs, suggesting that TE suppression, rather than the function of proteins, is the primary evolutionary force maintaining a subset of mRNAs as piRNA precursors. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved, general piRNA biogenesis mechanism that recognizes translating RNAs regardless of their ORF length in amniotes.

scholarly journals Long noncoding RNAs: fine-tuners hidden in the cancer signaling network

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shanshan Zhao ◽  
Xue Zhang ◽  
Shuo Chen ◽  
Song Zhang
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Biological Activities ◽  
Noncoding Rnas ◽  
Fine Tuning ◽  
Multiple Perspectives ◽  
Sequencing Technology ◽  
Protein Coding ◽  
Abnormal Signal ◽  
Non Coding Rnas

AbstractWith the development of sequencing technology, a large number of long non-coding RNAs (lncRNAs) have been identified in addition to coding genes. LncRNAs, originally considered as junk RNA, are dysregulated in various types of cancer. Although protein-coding signaling pathways underlie various biological activities, and abnormal signal transduction is a key trigger and indicator for tumorigenesis and cancer progression, lncRNAs are sparking keen interest due to their versatile roles in fine-tuning signaling pathways. We are just beginning to scratch the surface of lncRNAs. Therefore, despite the fact that lncRNAs drive malignant phenotypes from multiple perspectives, in this review, we focus on important signaling pathways modulated by lncRNAs in cancer to demonstrate an up-to-date understanding of this emerging field.

scholarly journals Transposable element-derived sequences in vertebrate development

Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ema Etchegaray ◽  
Magali Naville ◽  
Jean-Nicolas Volff ◽  
Zofia Haftek-Terreau
Keyword(s):  
Transposable Element ◽  
Genomic Instability ◽  
Adaptive Immunity ◽  
Insertion Site ◽  
Regulatory Sequences ◽  
Vertebrate Development ◽  
Genomic Context ◽  
Protein Coding ◽  
Evolutionary Success ◽  
Non Coding Rnas

AbstractTransposable elements (TEs) are major components of all vertebrate genomes that can cause deleterious insertions and genomic instability. However, depending on the specific genomic context of their insertion site, TE sequences can sometimes get positively selected, leading to what are called “exaptation” events. TE sequence exaptation constitutes an important source of novelties for gene, genome and organism evolution, giving rise to new regulatory sequences, protein-coding exons/genes and non-coding RNAs, which can play various roles beneficial to the host. In this review, we focus on the development of vertebrates, which present many derived traits such as bones, adaptive immunity and a complex brain. We illustrate how TE-derived sequences have given rise to developmental innovations in vertebrates and how they thereby contributed to the evolutionary success of this lineage.

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 Common Features in lncRNA Annotation and Classification: A Survey

2021 ◽  
Vol 7 (4) ◽  
pp. 77
Author(s):  
Christopher Klapproth ◽  
Rituparno Sen ◽  
Peter F. Stadler ◽  
Sven Findeiß ◽  
Jörg Fallmann
Keyword(s):  
Gene Expression ◽  
Disease Progression ◽  
In Silico ◽  
Therapeutic Targets ◽  
Untranslated Regions ◽  
Protein Coding ◽  
Coding Sequence ◽  
Common Features ◽  
Research Gap ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are widely recognized as important regulators of gene expression. Their molecular functions range from miRNA sponging to chromatin-associated mechanisms, leading to effects in disease progression and establishing them as diagnostic and therapeutic targets. Still, only a few representatives of this diverse class of RNAs are well studied, while the vast majority is poorly described beyond the existence of their transcripts. In this review we survey common in silico approaches for lncRNA annotation. We focus on the well-established sets of features used for classification and discuss their specific advantages and weaknesses. While the available tools perform very well for the task of distinguishing coding sequence from other RNAs, we find that current methods are not well suited to distinguish lncRNAs or parts thereof from other non-protein-coding input sequences. We conclude that the distinction of lncRNAs from intronic sequences and untranslated regions of coding mRNAs remains a pressing research gap.

scholarly journals A heterochromatin-specific RNA export pathway facilitates piRNA production

2019 ◽  
Author(s):  
Mostafa F. ElMaghraby ◽  
Peter Refsing Andersen ◽  
Florian Pühringer ◽  
Katharina Meixner ◽  
Thomas Lendl ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Mrna Export ◽  
Surveillance Systems ◽  
Rna Surveillance ◽  
Export Pathway ◽  
Transposon Silencing ◽  
Nuclear Rna ◽  
Rna Export ◽  
Non Coding Rnas ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) guide transposon silencing in animals. The 22-30nt piRNAs are processed in the cytoplasm from long non-coding RNAs. How piRNA precursors, which often lack RNA processing hallmarks of export-competent transcripts, achieve nuclear export is unknown. Here, we uncover the RNA export pathway specific for piRNA precursors in theDrosophilagermline. This pathway requires Nxf3-Nxt1, a variant of the hetero-dimeric mRNA export receptor Nxf1-Nxt1. Nxf3 interacts with UAP56, a nuclear RNA helicase essential for mRNA export, and CG13741/Bootlegger, which recruits Nxf3-Nxt1 and UAP56 to heterochromatic piRNA source loci. Upon RNA cargo binding, Nxf3 achieves nuclear export via the exportin Crm1, and accumulates together with Bootlegger in peri-nuclear nuage, suggesting that after export, Nxf3-Bootlegger delivers precursor transcripts to the piRNA processing sites. Our findings indicate that the piRNA pathway bypasses nuclear RNA surveillance systems to achieve export of heterochromatic, unprocessed transcripts to the cytoplasm, a strategy also exploited by retroviruses.

scholarly journals A community-driven roadmap to advance research on translated open reading frames detected by Ribo-seq

2021 ◽  
Author(s):  
Jonathan M Mudge ◽  
Jorge Ruiz-Orera ◽  
John R Prensner ◽  
Marie A Brunet ◽  
Jose Manuel Gonzalez ◽  
...  
Keyword(s):  
Gene Annotation ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Untranslated Regions ◽  
Biological Databases ◽  
Protein Coding ◽  
Circular Problem ◽  
Advance Research ◽  
Non Coding Rnas ◽  
Reading Frames

Ribosome profiling (Ribo-seq) has catalyzed a paradigm shift in our understanding of the translational vocabulary of the human genome, discovering thousands of translated open reading frames (ORFs) within long non-coding RNAs and presumed untranslated regions of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs due to uncertainties about their experimental reproducibility and physiological roles. Yet, it is indisputable that certain Ribo-seq ORFs make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unannotated by reference biological databases, this lack of characterisation will thwart research efforts examining their roles. Here, we outline the initial stages of a community-led effort supported by GENCODE / Ensembl, HGNC and UniProt to produce a consolidated catalog of human Ribo-seq ORFs.

scholarly journals baerhunter: an R package for the discovery and analysis of expressed non-coding regions in bacterial RNA-seq data

2019 ◽  
Author(s):  
A Ozuna ◽  
D Liberto ◽  
R M Joyce ◽  
K B Arnvig ◽  
I Nobeli
Keyword(s):  
Small Rnas ◽  
Real Data ◽  
R Package ◽  
Supplementary Information ◽  
Untranslated Regions ◽  
Rna Seq ◽  
Coding Regions ◽  
Bacterial Rna ◽  
Non Coding Rnas ◽  
Downstream Analysis

Abstract Summary Standard bioinformatics pipelines for the analysis of bacterial transcriptomic data commonly ignore non-coding but functional elements e.g. small RNAs, long antisense RNAs or untranslated regions (UTRs) of mRNA transcripts. The root of this problem is the use of incomplete genome annotation files. Here, we present baerhunter, a coverage-based method implemented in R, that automates the discovery of expressed non-coding RNAs and UTRs from RNA-seq reads mapped to a reference genome. The core algorithm is part of a pipeline that facilitates downstream analysis of both coding and non-coding features. The method is simple, easy to extend and customize and, in limited tests with simulated and real data, compares favourably against the currently most popular alternative. Availability and implementation The baerhunter R package is available from: https://github.com/irilenia/baerhunter Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Daphnia magna egg piRNA cluster expression profiles change as mothers age.

2021 ◽  
Author(s):  
Jack Hearn ◽  
Tom J Little
Keyword(s):  
Transposable Element ◽  
Daphnia Magna ◽  
Germ Line ◽  
Expression Profiles ◽  
Micro Rna ◽  
Older Mothers ◽  
Pirna Cluster ◽  
Non Coding Rnas ◽  
Pirna Pathway ◽  
F1 Generation

PiRNAs prevent transposable elements wreaking havoc on the germline genome. Changes in piRNA expression over the lifetime of an individual may impact on ageing through continued suppression, or release, of transposable element expression. We identified piRNA producing clusters in the genome of Daphnia magna by a combination of bioinformatic methods, and then contrasted their expression between parthenogenetically produced eggs representing maternally-deposited germline piRNAs of young (having their 1st clutch) and old (having their 5th clutch) mothers. Results from eggs were compared to cluster expression in three generations of adults. As for other arthropods, D. magna encodes long uni-directionally transcribed non-coding RNAs which consist of transposable element fragments which account for most piRNAs expressed. Egg tissues showed extensive differences between clutches from young mothers and those from old mothers, with 578 and 686 piRNA clusters upregulated, respectively, although most log fold-change differences for significant clusters were modest. When considering only highly expressed clusters, there was a bias towards 1st clutch eggs at 41 upregulated versus eight clusters in the eggs from older mothers. F0 generation differences between young and old mothers were fewer than eggs, as 179 clusters were up-regulated in young versus 170 old mothers. This dropped to 31 versus 22 piRNA clusters when comparing adults in the F1 generation, and no differences were detected in the F3 generation. These patterns were similar to that observed for D. magna micro-RNA expression. Little overlap in differentially expressed clusters was found between adults containing mixed somatic and germline (ovary) tissues and germ-line representing eggs. A cluster encompassing a Tudor domain containing gene important in the piRNA pathway was upregulated in the eggs from old mothers. We hypothesise that regulation of this gene this could form part of a feedback loop that reduces piRNA pathway activity explaining the reduced number of highly-expressed clusters in eggs from old mothers.

Long non-coding RNAs and human disease

2012 ◽  
Vol 40 (4) ◽  
pp. 902-906 ◽  
Author(s):  
Lorna W. Harries
Keyword(s):  
Human Disease ◽  
Fine Tuning ◽  
Protein Coding ◽  
Cellular Processes ◽  
Small Regulatory Rnas ◽  
Non Coding Rnas ◽  
Interfering Rna ◽  
Coding Potential ◽  
Eukaryotic Genomes

The central dogma of molecular biology states that DNA is transcribed into RNA, which in turn is translated into proteins. We now know, however, that as much as 50% of the transcriptome has no protein-coding potential, but rather represents an important class of regulatory molecules responsible for the fine-tuning of gene expression. Although the role of small regulatory RNAs [microRNAs and siRNAs (small interfering RNA)] is well defined, another much less characterized category of non-coding transcripts exists, namely lncRNAs (long non-coding RNAs). Pervasively expressed by eukaryotic genomes, lncRNAs can be kilobases long and regulate their targets by influencing the epigenetic control, chromatin status, mRNA processing or translation capacity of their targets. In the present review, I outline the potential mechanisms of action of lncRNAs, the cellular processes that have been associated with them, and also explore some of the emerging evidence for their involvement in common human disease.

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