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Green Synthesis of Nanoparticles in Oligonucleotide Drug Delivery System
Published in Yashwant Pathak, Gene Delivery, 2022
Manish P. Patel, Praful D. Bharadia, Kunjan B. Bodiwala, Mustakim M. Mansuri, Jayvadan Patel
Oligonucleotides are binding with RNA through DNA base pairing and modulate the function of the targeted RNA. It suggests a wide variety of oligonucleotides that modulate RNA through a different binding mechanisms (Esau et al., 2006). Briefly, these mechanisms can be classified largely as (a) those that bind to RNA and interfere with its function without promoting RNA degradation, such as translation arrest or modulating RNA processing (b) those that promote degradation of the RNA through endogenous enzymes, such as RNase H or argonaute-2 [RNA interference (RNAi)]. Recently, researchers have shown that Anti Sense Oligonucleotides can also be used to increase protein production, either through antagonizing microRNAs, which normally suppress protein production, or through masking upstream open reading frames (Liang et al., 2016). It shows that this drug delivery system has a huge impact in management or treatment of rare diseases.
Congenital Causes of Erythrocytosis/Polycythemias and Thrombocytosis
Published in Richard T. Silver, Ayalew Tefferi, Myeloproliferative Disorders, 2007
Josef T. Prchal, Radek C. Skoda
The production of TPO mRNA occurs at a constant rate and is not upregulated in situations with increased demand for platelet production, for example, thrombocytopenia induced by radiation or antibody lysis (31). Consistently, mice heterozygous for the TPO knockout allele have platelet counts intermediary to the homozygous knockout and wild type, demonstrating that the thrombocytopenia does not lead to a compensatory increase of transcription from the remaining wild-type locus (32). The production of Tpo protein is inhibited by a translational mechanism involving seven upstream open reading frames (uORFs) present in the 51-untranslated region (51-UTR) of the TPO mRNA (33). This mechanism pre-vents that pathologically high Tpo concentrations are reached under physiological conditions. Particularly, one uORF, designated uORF7, prevents the ribosomes from reaching the physiological start site for translation (33).
Mining for missed sORF-encoded peptides
Published in Expert Review of Proteomics, 2019
Xinqiang Yin, Yuanyuan Jing, Hanmei Xu
Current research work is mainly focused on model organisms and research on human sORFs and their encoded peptides. To search pathological organs or human tissues for SEPs may be helpful in understanding the pathological process of diseases. For example, recent studies have found that neoantigens, which are derived from non-mutated proteins to which T cell tolerance is incomplete or are entirely absent from the normal human genome and specifically expressed from tumor DNA, play an important role in cancer immunotherapy [124–129]. Many 5´upstream open reading frames (uORFs) have been identified in the human genome. The involvement of these uORFs in human pathologies has already been demonstrated [130,131]. A recent study revealed the key role of the translation of 5´ untranslated regions in cancer and exposed new targets for therapeutic intervention [129]. Another study reported that 5´ uORF-altering mutations dramatically decrease the expression of the downstream protein and can influence human phenotype and diseases [132].
Small, but mighty? Searching for human microproteins and their potential for understanding health and disease
Published in Expert Review of Proteomics, 2018
Annie Rathore, Thomas F. Martinez, Qian Chu, Alan Saghatelian
Pioneering studies of protein translation initiation first identified the presence of smORFs in the 5ʹ-untranslated regions (UTRs) of some mRNAs, which are commonly referred to as upstream open reading frames (uORFs) [4]. uORFs regulate the translation of downstream ORFs by engaging the ribosome before it initiates at the downstream ORF. Translation of downstream ORF is thought to occur through leaky scanning, whereby the first uORF initiation site is skipped, or by reinitiation of ribosome scanning upon reaching the end of the uORF [4]. Though initially thought to be unimportant, the translated sequence of the uORF was shown to matter in several cases. For instance, a uORF in the AdoMet carboxylase mRNA encodes a hexapeptide that when mutated effects the efficiency of translation repression of the downstream AdoMet carboxylase ORF [5]. This observation demonstrated that in some cases it is the interaction between the translated peptide and the ribosome that is mediating the activity of a uORF. More generally, this example and others like it show that uORFs/smORFs are translated and that the microproteins they encode are biologically active, providing the first evidence for functional microproteins. Since these findings smORFs have been identified in other noncoding regions [1], including 3ʹ-UTR and RNAs that were thought to be noncoding.