Association Analysis between Introns and mRNAs in Caenorhabditis elegans Genes with Different Expression Levels

2021 ◽  
Vol 16 ◽  
Author(s):  
Yanjuan Cao ◽  
Qiang Zhang ◽  
Zuwei Yan ◽  
Xiaoqing Zhao

Background: Introns are ubiquitous in pre-mRNA but are often overlooked. They also play an important role in the regulation of gene expression. Objective and Method : We mainly use the improved Smith-Waterman local alignment approach to compare the optimal matching regions between introns and mRNA sequences in Caenorhabditis elegans (C. elegans) genes with high and low expression. Results We found that the relative matching frequency distributions of all genes lie exactly between highly and lowly expressed genes, indicating that introns in highly and lowly expressed genes have different biological functions. Highly expressed genes have higher matching strengths on mRNA sequences than genes expressed at lower levels; the remarkably matched regions appear in UTR regions, particularly in the 3'UTR. The optimal matching frequency distributions have obvious differences in functional regions of the translation initiation and termination sites in highly and lowly expressed genes. The mRNA sequences with CpG islands tend to have stronger relative matching frequency distributions, especially in highly expressed genes. Additionally, the sequence characteristics of the optimal matched segments are consistent with those of the miRNAs, and they are considered a type of functional RNA segment. Conclusion: Introns in highly and lowly expressed genes contribute to the recognition translation initiation sites and translation termination sites. Moreover, our results suggest that the potential matching relationships between introns and mRNA sequences in highly and lowly expressed genes are significantly different and indicate that the matching strength correlates with the ability of introns to enhance gene expression.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.


BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Jessica Brunquell ◽  
Stephanie Morris ◽  
Yin Lu ◽  
Feng Cheng ◽  
Sandy D. Westerheide

2021 ◽  
Vol 8 ◽  
Author(s):  
Vandana Yadav ◽  
Inayat Ullah Irshad ◽  
Hemant Kumar ◽  
Ajeet K. Sharma

Quantitative prediction on protein synthesis requires accurate translation initiation and codon translation rates. Ribosome profiling data, which provide steady-state distribution of relative ribosome occupancies along a transcript, can be used to extract these rate parameters. Various methods have been developed in the past few years to measure translation-initiation and codon translation rates from ribosome profiling data. In the review, we provide a detailed analysis of the key methods employed to extract the translation rate parameters from ribosome profiling data. We further discuss how these approaches were used to decipher the role of various structural and sequence-based features of mRNA molecules in the regulation of gene expression. The utilization of these accurate rate parameters in computational modeling of protein synthesis may provide new insights into the kinetic control of the process of gene expression.


2018 ◽  
Vol 7 (1) ◽  
pp. 55
Author(s):  
Arash Matin Ahmadi ◽  
Hessamodin Ghasemi ◽  
Sajad Nooshin ◽  
Zoofa Zayani ◽  
Shohreh Zare Karizi ◽  
...  

Background: Aberrant promoter methylation of CpG islands is an important mechanism for regulation of gene expression. Recent data suggest that epigenetic abnormalities may occur very early in lung carcinogenesis. Systemic methylation changes may be a diagnostic marker for tumor development or prognosis. In this study, the expression and methylation of KMT2D and IGF2 genes were investigated in the lung cancer tissue compared to the adjacent normal tissue.Methods: The status of methylation of KMT2D and IGF2 genes were investigated in 30 patients with NSCLC after genomic DNA extraction using bisulfite treatment and MS-HRM method and the expression of these genes were checked by Real-Time PCR method in same samples.Results: For KMT2D gene, the expression and methylation level increased in 46.6% and 6.67% (respectively) for tumor samples comparison with normal samples (P>0.05). Also, for IGF2 gene 50% tumor samples overexpressed and 50% tumor samples showed that reduced expression comparison with the normal samples (P>0.05). In addition, 96.66% of tumor tissues did not show any change in methylation level for IGF2 gene promoter (P>0.05).Conclusion: This study showed that expression and methylation level of KMT2D and IGF2 genes did not change in NSCLC tumor samples compared to normal samples. However, this study was designed as a pilot study, and further investigations are required to confirm our findings.


Plants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 323
Author(s):  
Piotr Gawroński ◽  
Aleksandra Pałac ◽  
Lars B. Scharff

mRNA secondary structure can influence gene expression, e.g., by influencing translation initiation. The probing of in vivo mRNA secondary structures is therefore necessary to understand what determines the efficiency and regulation of gene expression. Here, in vivo mRNA secondary structure was analyzed using dimethyl sulfate (DMS)-MaPseq and compared to in vitro-folded RNA. We used an approach to analyze specific, full-length transcripts. To test this approach, we chose low, medium, and high abundant mRNAs. We included both monocistronic and multicistronic transcripts. Because of the slightly alkaline pH of the chloroplast stroma, we could probe all four nucleotides with DMS. The structural information gained was evaluated using the known structure of the plastid 16S rRNA. This demonstrated that the results obtained for adenosines and cytidines were more reliable than for guanosines and uridines. The majority of mRNAs analyzed were less structured in vivo than in vitro. The in vivo secondary structure of the translation initiation region of most tested genes appears to be optimized for high translation efficiency.


2021 ◽  
Author(s):  
Sandy D. Westerheide ◽  
Doreen I. Lugano ◽  
Andrew Deonarine ◽  
Margaret A. Park

The Cell Division Cycle and Apoptosis Regulator (CCAR) protein family members are putative transcription regulators that have been characterized for modulating the cell cycle, apoptosis, metabolism, and the heat shock response. Mammals have two CCAR family members, CCAR1 and CCAR2/DBC1, that evolved from the founding family member CCAR-1 that is expressed in Caenorhabditis elegans. Mammalian CCAR2, the most well-studied family member, has been shown to regulate genes involved in metabolism in cultured cells. However, the regulation of gene expression by CCAR family members at an organismal level is unknown. Here, we use whole transcriptome RNA sequencing to examine the effects of CCAR-1 on gene expression in Caenorhabditis elegans. We show that CCAR-1 regulates germline transcription, reproduction, lifespan, and DNA-damage induced apoptosis. This study shows the role of CCAR-1 in vital physiological functions in the C. elegans germline that have not been investigated before.


2017 ◽  
Author(s):  
Sai Zhang ◽  
Hailin Hu ◽  
Tao Jiang ◽  
Lei Zhang ◽  
Jianyang Zeng

AbstractMotivationTranslation initiation is a key step in the regulation of gene expression. In addition to the annotated translation initiation sites (TISs), the translation process may also start at multiple alternative TISs (including both AUG and non-AUG codons), which makes it challenging to predict TISs and study the underlying regulatory mechanisms. Meanwhile, the advent of several high-throughput sequencing techniques for profiling initiating ribosomes at single-nucleotide resolution, e.g., GTI-seq and QTI-seq, provides abundant data for systematically studying the general principles of translation initiation and the development of computational method for TIS identification.MethodsWe have developed a deep learning based framework, named TITER, for accurately predicting TISs on a genome-wide scale based on QTI-seq data. TITER extracts the sequence features of translation initiation from the surrounding sequence contexts of TISs using a hybrid neural network and further integrates the prior preference of TIS codon composition into a unified prediction framework.ResultsExtensive tests demonstrated that TITER can greatly outperform the state-of-the-art prediction methods in identifying TISs. In addition, TITER was able to identify important sequence signatures for individual types of TIS codons, including a Kozak-sequence-like motif for AUG start codon. Furthermore, the TITER prediction score can be related to the strength of translation initiation in various biological scenarios, including the repressive effect of the upstream open reading frames (uORFs) on gene expression and the mutational effects influencing translation initiation efficiency.AvailabilityTITER is available as an open-source software and can be downloaded from https://github.com/zhangsaithu/[email protected] and [email protected]


Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Katherine A Maniates ◽  
Benjamin S Olson ◽  
Allison L Abbott

Abstract Posttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates. In Caenorhabditis elegans hermaphrodites, cell fate decisions are made for germline sex determination during larval development when sperm are generated in a short window before the switch to oocyte production. Here, analysis of newly generated mir-44 family mutants has identified a family of miRNAs that modulate the germline sex determination pathway in C. elegans. Mutants with the loss of mir-44 and mir-45 produce fewer sperm, showing both a delay in the specification and formation of sperm as well as an early termination of sperm specification accompanied by a premature switch to oocyte production. mir-44 and mir-45 are necessary for the normal period of fog-1 expression in larval development. Through genetic analysis, we find that mir-44 and mir-45 may act upstream of fbf-1 and fem-3 to promote sperm specification. Our research indicates that the mir-44 family promotes sperm cell fate specification during larval development and identifies an additional posttranscriptional regulator of the germline sex determination pathway.


Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3275-3283 ◽  
Author(s):  
G. Seydoux ◽  
S. Strome

One hundred years after Weismann's seminal observations, the mechanisms that distinguish the germline from the soma still remain poorly understood. This review describes recent studies in Caenorhabditis elegans, which suggest that germ cells utilize unique mechanisms to regulate gene expression. In particular, mechanisms that repress the production of mRNAs appear to be essential to maintain germ cell fate and viability.


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