Two Specific Groups of Nhc Proteins Involved in Gene Expression *
Isaac Bekhor, Carol J. Mirell, C. C. Liew in Progress in Nonhistone Protein Research, 1985
In view of recent findings in immunoglobulin genes,47 oncogenes,48,49 and calcitonin gene structure,50 it has become evident that the DNA sequence by itself can mediate gene expression. However, the question remains as to why all cell types containing the same DNA information exhibit different cell-specific gene expression. For example, neuroendocrine genes are expressed only in nerve cells, not in other cell types. We believe that the interaction of chromatin proteins with nucleic acids must play an active role in gene expression. At least two groups of NHC proteins, which have been examined in our laboratory, provide evidence for this contention. One group of proteins is that known to be involved in the processing of mRNA maturation, i.e., the proteins associated with heterogeneous nuclear RNA (hnRNA).51–54 The second is the group associated with active chromatin (i.e., the highly phosphorylated proteins) already discussed in this report.
Marvellous molecules
Brendan Curran in A Terrible Beauty is Born, 2020
Despite the fact that the principles of gene expression are fundamentally similar in bacteria (Figure 8.2) and humans, there are actually two basic differences which prevent human genes from being decoded by the bacterium without a great deal of prior manipulation. First, promoter sequences in human genes are not recognised by the bacterial transcription factors and RNA polymerase that regulate the production of messenger RNA molecules; this prevents human genetic information being transcribed in bacteria. Second, the genes of all multi-cellular organisms (humans included) have sections (called introns) which are not actually decoded. This means that the primary transcript has to be ‘edited’ (‘spliced’ is the word often used) to remove the introns and produce a mature RNA before it is used by the ribosomes to assemble the encoded protein. Bacteria do not have this system for splicing the messenger RNA and so are unable to process human gene messenger RNAs for use by their ribosomes.
Disease Prediction and Drug Development
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam in Introduction to Computational Health Informatics, 2019
During the transcription process, a transcriptase binds to the promoter-region, strips the hydrogen bonds between the A≡T and G≡C pairs and separates the strand. In the next phase, a thymine molecule (“T”) is substituted by an uracil (“U”) molecule. The transcription of a bacterial gene is straightforward due to the absence of introns. However, in eukaryotes, the primary transcript after the transcription process also includes the corresponding intron version. The primary transcript goes through an additional process of splicing that removes the intron-part from the primary transcript and joins the exons to create the corresponding mRNA. The process of transcription of DNA to mRNA for eukaryotic gene is illustrated in Figure 10.5.
RNA therapeutics for retinal diseases
Published in Expert Opinion on Biological Therapy, 2021
Michael C Gemayel, Ashay D. Bhatwadekar, Thomas Ciulla
miRNAs are transcribed in the nucleus, often with genes of functionally related miRNA clustered on the same chromosome and expressed as a single primary transcript (pri-miRNA). Double-stranded short hairpin structures are contained within the pri-miRNA and are recognized in the nucleus by a protein complex with resulting cleavage by the RNAse III-type enzyme, Drosha, resulting in precursor miRNA (pre-miRNA). The pre-miRNA is then transported to the cytosol through the nuclear pore complex by exportin5, where final cleavage by another RNAse III-type enzyme, called Dicer, takes place. This results in a double-strand miRNA, where one strand then interacts, and is bound to argonaute (AGO) proteins, which are then assembled to form an RNA-Induced silencing complex (RISC). Through the miRNA ‘guide strand,’ this complex is then guided to target mRNA through imperfectly complementary target sites, usually in the 3ʹ-untranslated region (UTR), with resulting repression of its translation [9,12].
Antisense Oligonucleotide Therapy for Ophthalmic Conditions
Published in Seminars in Ophthalmology, 2021
Kevin Ferenchak, Iris Deitch, Rachel Huckfeldt
A review of the pathway from gene to protein is helpful in understanding the mechanism of AON. Genes are composed of introns and exons, and exons are the sequences of base pairs that are expressed. DNA is transcribed in the nucleus to a complementary strand of pre-mRNA. Before leaving the nucleus, non-coding intronic regions are excised from this primary transcript and exons are spliced together at a spliceosome. The mRNA is then transported to the cytoplasm where it is translated on ribosomes in sets of three bases into amino acids, which aggregate to form proteins that are critical for the health and function of a cell. Misspellings of even a single base pair can cause a pathogenic shift in the sequence of amino acids, leading to aberrant splicing and a malfunctioning protein. Studies have estimated that more than 10% of genetic disorders are caused by single base pair mutations at exon-intron junctions that alter splicing.14,15 Alterations in both exons and introns can be associated with pathogenic changes in the genetic sequence such as nonsense mutation causing a premature termination, missense mutations changing an amino acid, and frameshift mutations caused by insertion or deletion of a set of base pairs not divisible by three, thus altering every amino acid downstream.
Involvement of miRNAs in cellular responses to radiation
Published in International Journal of Radiation Biology, 2022
Joanna Rzeszowska-Wolny, Dorota Hudy, Krzysztof Biernacki, Sylwia Ciesielska, Roman Jaksik
MiRNAs are single-stranded, non-coding regulatory RNAs built usually from 21-23 nucleotides which associate with Argonaute (AGO) proteins forming RNA- induced silencing complexes (RISCs), which serve as post-transcriptional regulators of many genes. MiRNAs arise by a quite complicated biogenesis pathway divided into a few main phases starting from a transcription of a primary transcript (pri-miRNA) by RNA polymerase II or III (Lee et al. 2004; Borchert et al. 2006; Ha and Kim 2014) which is processed to a shorter form (pre-miRNA); both these steps are carried out in the nucleus (Figure 1). The conversion of pri-miRNAs into pre-miRNAs is carried out with the help of the Drosha-DGCR8 complex, and the pre-miRNAs are then transported to the cytoplasm by Exportin 5 (XPO5) where they are processed to mature, double-stranded ∼20 nucleotides long miRNA-miRNA* (Borchert et al. 2006; Bumgarner 2013; Ha and Kim 2014). One strand of this double-stranded miRNA molecule is loaded into one of the AGO proteins, forming a RISC. Digestion of pre-mi-RNA to its mature form and loading into AGO needs the enzyme Dicer, part of a protein complex containing two double-stranded RNA-binding proteins TRBP and PRKRA (Chendrimada et al. 2005; Borchert et al. 2006; Bumgarner 2013; Ha and Kim 2014) (reviewed in (Kurzynska-Kokorniak et al. 2015). AGO proteins may further interact with others to form complexes containing, among others, members of the trinucleotide repeat-containing 6 protein family (TNRC6) which seem to be the most important for miRNA-induced regulation of translation because they create a platform for further proteins and formation of differently composed RISCs (Borchert et al. 2006; Huntzinger and Izaurralde 2011; Bumgarner 2013; Ha and Kim 2014; Mathys et al. 2014).
Related Knowledge Centers
- DNA
- Ribosomal Rna
- Rna
- Transfer Rna
- Messenger Rna
- Cell Nucleus
- Transcription
- Translation
- Post-Transcriptional Modification
- Mature Messenger Rna