scholarly journals lncRNAs in development and differentiation: from sequence motifs to functional characterization

Development ◽  
2021 ◽  
Vol 148 (1) ◽  
pp. dev182741
Author(s):  
Florian Constanty ◽  
Alena Shkumatava
Keyword(s):  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Sequence Motifs ◽  
Cellular Functions ◽  
Rna Motifs ◽  
Rna Sequences ◽  
Conserved Sequence ◽  
Interaction Partners ◽  
Sequence Elements ◽  
Development And Differentiation

ABSTRACTThe number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners.

scholarly journals Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ami Shah ◽  
Madison Ratkowski ◽  
Alessandro Rosa ◽  
Paul Feinstein ◽  
Thomas Bozza
Keyword(s):  
Gene Expression ◽  
Large Family ◽  
Sequence Motifs ◽  
Specific Expression ◽  
Cis Acting ◽  
Conserved Sequence ◽  
Trace Amine ◽  
Sequence Elements ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

AbstractOlfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

scholarly journals Characterization of PPTNs, a Cyanobacterial Phosphopantetheinyl Transferase from Nodularia spumigena NSOR10

2007 ◽  
Vol 189 (8) ◽  
pp. 3133-3139 ◽  
Author(s):  
J. N. Copp ◽  
A. A. Roberts ◽  
M. A. Marahiel ◽  
B. A. Neilan
Keyword(s):  
Acyl Carrier Protein ◽  
Functional Characterization ◽  
Bioactive Metabolites ◽  
Sequence Motifs ◽  
Phosphopantetheinyl Transferase ◽  
Carrier Proteins ◽  
Nodularia Spumigena ◽  
Conserved Sequence ◽  
Wide Range

ABSTRACT The phosphopantetheinyl transferases (PPTs) are a superfamily of essential enzymes required for the synthesis of a wide range of compounds, including fatty acids, polyketides, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways by transfer of a phosphopantetheinyl moiety. The diverse PPT superfamily can be divided into two families based on specificity and conserved sequence motifs. The first family is typified by the Escherichia coli acyl carrier protein synthase (AcpS), which is involved in fatty acid synthesis. The prototype of the second family is the broad-substrate-range PPT Sfp, which is required for surfactin biosynthesis in Bacillus subtilis. Most cyanobacteria do not encode an AcpS-like PPT, and furthermore, some of their Sfp-like PPTs belong to a unique phylogenetic subgroup defined by the PPTs involved in heterocyst differentiation. Here, we describe the first functional characterization of a cyanobacterial PPT based on a structural analysis and subsequent functional analysis of the Nodularia spumigena NSOR10 PPT. Southern hybridizations suggested that this enzyme may be the only PPT encoded in the N. spumigena NSOR10 genome. Expression and enzyme characterization showed that this PPT was capable of modifying carrier proteins resulting from both heterocyst glycoplipid synthesis and nodularin toxin synthesis. Cyanobacteria are a unique and vast source of bioactive metabolites; therefore, an understanding of cyanobacterial PPTs is important in order to harness the biotechnological potential of cyanobacterial natural products.

scholarly journals Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter.

1989 ◽  
Vol 9 (2) ◽  
pp. 747-756 ◽  
Author(s):  
L Poellinger ◽  
R G Roeder
Keyword(s):  
Transcription Factors ◽  
Heavy Chain ◽  
Protein Interactions ◽  
Transcription Initiation ◽  
Immunoglobulin Heavy Chain ◽  
Sequence Motifs ◽  
Cell Type Specificity ◽  
Conserved Sequence ◽  
Octamer Motif ◽  
Sequence Elements

Immunoglobulin heavy-chain genes contain two conserved sequence elements 5' to the site of transcription initiation: the octamer ATGCAAAT and the heptamer CTCATGA. Both of these elements are required for normal cell-specific promoter function. The present study demonstrates that both the ubiquitous and lymphoid-cell-specific octamer transcription factors (OTF-1 and OTF-2, respectively) interact specifically with each of the two conserved sequence elements, forming either homo- or heterodimeric complexes. This was surprising, since the heptamer and octamer sequence motifs bear no obvious similarity to each other. Binding of either factor to the octamer element occurred independently. However, OTF interaction with the heptamer sequence appeared to require the presence of an intact octamer motif and occurred with a spacing of either 2 or 14 base pairs between the two elements, suggesting coordinate binding resulting from protein-protein interactions. The degeneracy in sequences recognized by the OTFs may be important in widening the range over which gene expression can be modulated and in establishing cell type specificity.

scholarly journals The evolution of hemocyanin genes in Tectipleura: a multitude of conserved introns in highly diverse gastropods

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriela Giannina Schäfer ◽  
Veronika Pedrini-Martha ◽  
Daniel John Jackson ◽  
Reinhard Dallinger ◽  
Bernhard Lieb
Keyword(s):  
Molecular Mechanisms ◽  
Lymnaea Stagnalis ◽  
Helix Pomatia ◽  
Oxygen Affinity ◽  
Sister Group ◽  
Pomacea Canaliculata ◽  
Sequence Motifs ◽  
Conserved Sequence ◽  
Intron Number ◽  
Gene Structures

Abstract Background Hemocyanin is the oxygen transporter of most molluscs. Since the oxygen affinity of hemocyanin is strongly temperature-dependent, this essential protein needs to be well-adapted to the environment. In Tectipleura, a very diverse group of gastropods with > 27,000 species living in all kinds of habitats, several hemocyanin genes have already been analyzed. Multiple independent duplications of this gene have been identified and may represent potential adaptations to different environments and lifestyles. The aim of this study is to further explore the evolution of these genes by analyzing their exon–intron architectures. Results We have reconstructed the gene architectures of ten hemocyanin genes from four Tectipleura species: Aplysia californica, Lymnaea stagnalis, Cornu aspersum and Helix pomatia. Their hemocyanin genes each contain 53 introns, significantly more than in the hemocyanin genes of Cephalopoda (9–11), Vetigastropoda (15) and Caenogastropoda (28–33). The gene structures of Tectipleura hemocyanins are identical in terms of intron number and location, with the exception of one out of two hemocyanin genes of L. stagnalis that comprises one additional intron. We found that gene structures that differ between molluscan lineages most probably evolved more recently through independent intron gains. Conclusions The strict conservation of the large number of introns in Tectipleura hemocyanin genes over 200 million years suggests the influence of a selective pressure on this gene structure. While we could not identify conserved sequence motifs within these introns, it may be simply the great number of introns that offers increased possibilities of gene regulation relative to hemocyanin genes with less introns and thus may have facilitated habitat shifts and speciation events. This hypothesis is supported by the relatively high number of introns within the hemocyanin genes of Pomacea canaliculata that has evolved independently of the Tectipleura. Pomacea canaliculata belongs to the Caenogastropoda, the sister group of Heterobranchia (that encompass Tectipleura) which is also very diverse and comprises species living in different habitats. Our findings provide a hint to some of the molecular mechanisms that may have supported the spectacular radiation of one of Metazoa’s most species rich groups.

scholarly journals Amino Acid Sequence Motifs Essential for P0-Mediated Suppression of RNA Silencing in an Isolate of Potato leafroll virus from Inner Mongolia

2014 ◽  
Vol 27 (6) ◽  
pp. 515-527 ◽  
Author(s):  
Tao Zhuo ◽  
Yuan-Yuan Li ◽  
Hai-Ying Xiang ◽  
Zhan-Yu Wu ◽  
Xian-Bin Wang ◽  
...  
Keyword(s):  
Rna Silencing ◽  
Molecular Mechanisms ◽  
Alternative Pathway ◽  
Potato Leafroll Virus ◽  
Sequence Motifs ◽  
Suppressor Activity ◽  
Conserved Sequence ◽  
Complex Protein ◽  
Proteasome Pathway ◽  
Leafroll Virus

Polerovirus P0 suppressors of host gene silencing contain a consensus F-box-like motif with Leu/Pro (L/P) requirements for suppressor activity. The Inner Mongolian Potato leafroll virus (PLRV) P0 protein (P0PL-IM) has an unusual F-box-like motif that contains a Trp/Gly (W/G) sequence and an additional GW/WG-like motif (G139/W140/G141) that is lacking in other P0 proteins. We used Agrobacterium infiltration-mediated RNA silencing assays to establish that P0PL-IM has a strong suppressor activity. Mutagenesis experiments demonstrated that the P0PL-IM F-box-like motif encompasses amino acids 76-LPRHLHYECLEWGLLCG THP-95, and that the suppressor activity is abolished by L76A, W87A, or G88A substitution. The suppressor activity is also weakened substantially by mutations within the G139/W140/G141 region and is eliminated by a mutation (F220R) in a C-terminal conserved sequence of P0PL-IM. As has been observed with other P0 proteins, P0PL-IM suppression is correlated with reduced accumulation of the host AGO1-silencing complex protein. However, P0PL-IM fails to bind SKP1, which functions in a proteasome pathway that may be involved in AGO1 degradation. These results suggest that P0PL-IM may suppress RNA silencing by using an alternative pathway to target AGO1 for degradation. Our results help improve our understanding of the molecular mechanisms involved in PLRV infection.

scholarly journals The Cellular Functions and Molecular Mechanisms of G-Quadruplex Unwinding Helicases in Humans

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Liu ◽  
Xinting Zhu ◽  
Kejia Wang ◽  
Bo Zhang ◽  
Shuyi Qiu
Keyword(s):  
Molecular Mechanisms ◽  
Secondary Structures ◽  
Biological Processes ◽  
Cellular Functions ◽  
General Introduction ◽  
Rna Sequences ◽  
Study Methods ◽  
G Quadruplex ◽  
And Function

G-quadruplexes (G4s) are stable non-canonical secondary structures formed by G-rich DNA or RNA sequences. They play various regulatory roles in many biological processes. It is commonly agreed that G4 unwinding helicases play key roles in G4 metabolism and function, and these processes are closely related to physiological and pathological processes. In recent years, more and more functional and mechanistic details of G4 helicases have been discovered; therefore, it is necessary to carefully sort out the current research efforts. Here, we provide a systematic summary of G4 unwinding helicases from the perspective of functions and molecular mechanisms. First, we provide a general introduction about helicases and G4s. Next, we comprehensively summarize G4 unfolding helicases in humans and their proposed cellular functions. Then, we review their study methods and molecular mechanisms. Finally, we share our perspective on further prospects. We believe this review will provide opportunities for researchers to reach the frontiers in the functions and molecular mechanisms of human G4 unwinding helicases.

Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter

1989 ◽  
Vol 9 (2) ◽  
pp. 747-756
Author(s):  
L Poellinger ◽  
R G Roeder
Keyword(s):  
Transcription Factors ◽  
Heavy Chain ◽  
Protein Interactions ◽  
Transcription Initiation ◽  
Immunoglobulin Heavy Chain ◽  
Sequence Motifs ◽  
Cell Type Specificity ◽  
Conserved Sequence ◽  
Octamer Motif ◽  
Sequence Elements

Immunoglobulin heavy-chain genes contain two conserved sequence elements 5' to the site of transcription initiation: the octamer ATGCAAAT and the heptamer CTCATGA. Both of these elements are required for normal cell-specific promoter function. The present study demonstrates that both the ubiquitous and lymphoid-cell-specific octamer transcription factors (OTF-1 and OTF-2, respectively) interact specifically with each of the two conserved sequence elements, forming either homo- or heterodimeric complexes. This was surprising, since the heptamer and octamer sequence motifs bear no obvious similarity to each other. Binding of either factor to the octamer element occurred independently. However, OTF interaction with the heptamer sequence appeared to require the presence of an intact octamer motif and occurred with a spacing of either 2 or 14 base pairs between the two elements, suggesting coordinate binding resulting from protein-protein interactions. The degeneracy in sequences recognized by the OTFs may be important in widening the range over which gene expression can be modulated and in establishing cell type specificity.

scholarly journals DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome

2021 ◽  
Author(s):  
Yanrong Ji ◽  
Zhihan Zhou ◽  
Han Liu ◽  
Ramana V Davuluri
Keyword(s):  
Dna Sequences ◽  
Regulatory Elements ◽  
Ease Of Use ◽  
Fine Tuning ◽  
Supplementary Information ◽  
Sequence Motifs ◽  
Semantic Relationship ◽  
Accurate Identification ◽  
Conserved Sequence ◽  
Genome Wide

Abstract Motivation Deciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. Results To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, to capture global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We compared DNABERT to the most widely used programs for genome-wide regulatory elements prediction and demonstrate its ease of use, accuracy and efficiency. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on prediction of promoters, splice sites and transcription factor binding sites, after easy fine-tuning using small task-specific labeled data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variant candidates. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance. We anticipate that the pre-trained DNABERT model can be fined tuned to many other sequence analyses tasks. Availability and implementation The source code, pretrained and finetuned model for DNABERT are available at GitHub (https://github.com/jerryji1993/DNABERT). Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 332
Author(s):  
Valentina Brillo ◽  
Leonardo Chieregato ◽  
Luigi Leanza ◽  
Silvia Muccioli ◽  
Roberto Costa
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Eukaryotic Cells ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Mitochondrial Ros ◽  
Intracellular Organelles ◽  
Proliferation Regulation ◽  
Dynamic Plasticity

Mitochondria are key intracellular organelles involved not only in the metabolic state of the cell, but also in several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these organelles are characterized by continuous events of fission and fusion which contribute to the dynamic plasticity of their network, also strongly influenced by mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount of reactive oxygen species (ROS) inside eukaryotic cells, which are reported to mediate a plethora of both physiological and pathological cellular functions, such as growth and proliferation, regulation of autophagy, apoptosis, and metastasis. Therefore, targeting mitochondrial ROS could be a promising strategy to overcome and hinder the development of diseases such as cancer, where malignant cells, possessing a higher amount of ROS with respect to healthy ones, could be specifically targeted by therapeutic treatments. In this review, we collected the ultimate findings on the blended interplay among mitochondrial shaping, mitochondrial ROS, and several signaling pathways, in order to contribute to the dissection of intracellular molecular mechanisms involved in the pathophysiology of eukaryotic cells, possibly improving future therapeutic approaches.

scholarly journals Deciphering the Mounting Complexity of the p53 Regulatory Network in Correlation to Long Non-Coding RNAs (lncRNAs) in Ovarian Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 527 ◽  
Author(s):  
Sonali Pal ◽  
Manoj Garg ◽  
Amit Kumar Pandey
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Critical Role ◽  
Functional Characterization ◽  
Great Promise ◽  
Altered Expression ◽  
Disease Biology ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.

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