Noncoding RNAs in eukaryotic ribosome biogenesis and function

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

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Commuting to Work: Nucleolar Long Non-Coding RNA Control Ribosome Biogenesis from Near and Far

Non-Coding RNA ◽

10.3390/ncrna7030042 ◽

2021 ◽

Vol 7 (3) ◽

pp. 42

Author(s):

Victoria Mamontova ◽

Barbara Trifault ◽

Lea Boten ◽

Kaspar Burger

Keyword(s):

Gene Expression ◽

Rna Polymerase Ii ◽

Ribosome Biogenesis ◽

Intergenic Spacer ◽

Cellular Growth ◽

Rrna Synthesis ◽

Protein Coding ◽

Non Coding Rna ◽

And Function ◽

In Cis

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.

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Ubiquitin and Ubiquitin-Like Proteins and Domains in Ribosome Production and Function: Chance or Necessity?

International Journal of Molecular Sciences ◽

10.3390/ijms22094359 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4359

Author(s):

Sara Martín-Villanueva ◽

Gabriel Gutiérrez ◽

Dieter Kressler ◽

Jesús de la Cruz

Keyword(s):

Ribosomal Proteins ◽

Ribosome Biogenesis ◽

Ribosome Assembly ◽

Cellular Processes ◽

Substrate Protein ◽

Precursor Proteins ◽

Assembly Factors ◽

Ubiquitin Moiety ◽

And Function

Ubiquitin is a small protein that is highly conserved throughout eukaryotes. It operates as a reversible post-translational modifier through a process known as ubiquitination, which involves the addition of one or several ubiquitin moieties to a substrate protein. These modifications mark proteins for proteasome-dependent degradation or alter their localization or activity in a variety of cellular processes. In most eukaryotes, ubiquitin is generated by the proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor, or as a single N-terminal moiety to ribosomal proteins, which are practically invariably eL40 and eS31. Herein, we summarize the contribution of the ubiquitin moiety within precursors of ribosomal proteins to ribosome biogenesis and function and discuss the biological relevance of having maintained the explicit fusion to eL40 and eS31 during evolution. There are other ubiquitin-like proteins, which also work as post-translational modifiers, among them the small ubiquitin-like modifier (SUMO). Both ubiquitin and SUMO are able to modify ribosome assembly factors and ribosomal proteins to regulate ribosome biogenesis and function. Strikingly, ubiquitin-like domains are also found within two ribosome assembly factors; hence, the functional role of these proteins will also be highlighted.

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Identification and function annotation of long intervening noncoding RNAs

Briefings in Bioinformatics ◽

10.1093/bib/bbw046 ◽

2016 ◽

pp. bbw046 ◽

Cited By ~ 8

Author(s):

Haitao Luo ◽

Dechao Bu ◽

Liang Sun ◽

Shuangsang Fang ◽

Zhiyong Liu ◽

...

Keyword(s):

Noncoding Rnas ◽

Function Annotation ◽

And Function

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Construction of an lncRNA–mRNA Co-Expression Regulatory Network Mediating Inflammation and Regeneration Following Acute Pancreatitis Injury

10.21203/rs.3.rs-1152574/v1 ◽

2021 ◽

Author(s):

Jing Wang ◽

Tianjie Chen ◽

Xiaohua Zhang ◽

Shulei Zhao

Keyword(s):

Acute Pancreatitis ◽

Mrna Expression ◽

Regulatory Network ◽

Noncoding Rnas ◽

Pancreatic Injury ◽

Control Group ◽

Rna Seq ◽

Damage Repair ◽

Injury And Repair ◽

And Function

Abstract Long noncoding RNAs (lncRNAs) play important roles in the occurrence and development of many diseases and can be used as targets for diagnosis and treatment. However, the expression and function of lncRNAs in the injury and repair of acute pancreatitis (AP) are unclear. To decipher lncRNAs’ regulatory roles in AP, we reanalyzed an RNA-seq dataset of 24 pancreatic tissues, including those of normal control mice (BL), those 7 days after mild AP (D7), and those 14 days after mild AP (D14). The results showed significant differences in lncRNA and mRNA expression of D7/D14 groups compared with the control group. Co-expression analysis showed that differentially expressed (DE) lncRNAs were closely related to immunity- and inflammation-related pathways by trans-regulating mRNA expression. The lncRNA–mRNA network showed that the lncRNAs Dancer, Gmm20488, Terc, Snhg3, and Snhg20 were significantly correlated with AP pathogenesis. WGCNA and cis regulation analysis also showed that AP repair-associated lncRNAs were correlated with extracellular and inflammation-related genes, which affect the repair and regeneration of pancreatic injury after AP. In conclusion, the systemic dysregulation of lncRNAs is strongly involved in remodeling AP’s gene expression regulatory network, and the lncRNA–mRNA expression network could identify targets for AP treatment and damage repair.

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The Roles of Long Noncoding RNAs HNF1α-AS1 and HNF4α-AS1 in Drug Metabolism and Human Diseases

Non-Coding RNA ◽

10.3390/ncrna6020024 ◽

2020 ◽

Vol 6 (2) ◽

pp. 24 ◽

Cited By ~ 1

Author(s):

Liming Chen ◽

Yifan Bao ◽

Suzhen Jiang ◽

Xiao-bo Zhong

Keyword(s):

Drug Metabolism ◽

Drug Toxicity ◽

Target Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Future Directions ◽

Protein Coding ◽

Mirna Sponge ◽

Current Review ◽

And Function

Long noncoding RNAs (lncRNAs) are RNAs with a length of over 200 nucleotides that do not have protein-coding abilities. Recent studies suggest that lncRNAs are highly involved in physiological functions and diseases. lncRNAs HNF1α-AS1 and HNF4α-AS1 are transcripts of lncRNA genes HNF1α-AS1 and HNF4α-AS1, which are antisense lncRNA genes located in the neighborhood regions of the transcription factor (TF) genes HNF1α and HNF4α, respectively. HNF1α-AS1 and HNF4α-AS1 have been reported to be involved in several important functions in human physiological activities and diseases. In the liver, HNF1α-AS1 and HNF4α-AS1 regulate the expression and function of several drug-metabolizing cytochrome P450 (P450) enzymes, which also further impact P450-mediated drug metabolism and drug toxicity. In addition, HNF1α-AS1 and HNF4α-AS1 also play important roles in the tumorigenesis, progression, invasion, and treatment outcome of several cancers. Through interacting with different molecules, including miRNAs and proteins, HNF1α-AS1 and HNF4α-AS1 can regulate their target genes in several different mechanisms including miRNA sponge, decoy, or scaffold. The purpose of the current review is to summarize the identified functions and mechanisms of HNF1α-AS1 and HNF4α-AS1 and to discuss the future directions of research of these two lncRNAs.

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Expanding Role of Ubiquitin in Translational Control

International Journal of Molecular Sciences ◽

10.3390/ijms21031151 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1151 ◽

Cited By ~ 3

Author(s):

Shannon E. Dougherty ◽

Austin O. Maduka ◽

Toshifumi Inada ◽

Gustavo M. Silva

Keyword(s):

Translational Control ◽

Ribosomal Proteins ◽

Ribosome Biogenesis ◽

Rna Binding ◽

Protein Quality ◽

Rna Binding Proteins ◽

Ubiquitin Chain ◽

Molecular Aspects ◽

And Function

The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.

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Current Research Progress on Long Noncoding RNAs Associated with Hepatocellular Carcinoma

Analytical Cellular Pathology ◽

10.1155/2019/1534607 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Haihong Shi ◽

Yuxin Xu ◽

Xin Yi ◽

Dandan Fang ◽

Xia Hou

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Liver Cancer ◽

Biological Activities ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Research Progress ◽

Invasion And Metastasis ◽

Complex Processes ◽

And Function

Hepatocellular carcinoma (HCC) is the second leading cause of mortality among cancers. It has been found that long noncoding RNAs (lncRNAs) are involved in many human cancers, including liver cancer. It has been identified that carcinogenic and tumor-suppressing lncRNAs are associated with complex processes in liver cancer. These lncRNAs may participate in a variety of pathological and biological activities, such as cell proliferation, apoptosis, invasion, and metastasis. Here, we review the regulation and function of lncRNA in liver cancer and evaluate the potential of lncRNA as a new goal for liver cancer.

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Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism

Biological Chemistry ◽

10.1515/hsz-2013-0153 ◽

2013 ◽

Vol 394 (9) ◽

pp. 1133-1143 ◽

Cited By ~ 17

Author(s):

Kaspar Burger ◽

Dirk Eick

Keyword(s):

Ribosomal Rna ◽

Ribosome Biogenesis ◽

Rna Metabolism ◽

Chemotherapeutic Drugs ◽

Tumor Suppressor P53 ◽

Nucleolar Structure ◽

Highly Sensitive ◽

Important Regulator ◽

Sensitive Sensor ◽

And Function

Abstract The production and processing of ribosomal RNA is a complex and well-coordinated nucleolar process for ribosome biogenesis. Progress in understanding nucleolar structure and function has lead to the unexpected discovery of the nucleolus as a highly sensitive sensor of cellular stress and an important regulator of the tumor suppressor p53. Inhibition of ribosomal RNA metabolism has been shown to activate a signaling pathway for p53 induction. This review elucidates the potential of classical and recently developed chemotherapeutic drugs to stabilize p53 by inhibiting nucleolar functions.

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