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Small noncoding RNAs as biomarkers for pregnancy complications
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Liron Yoffe, Meitar Grad, Avital Luba Polsky, Moshe Hod, Noam Shomron
Small noncoding RNAs (ncRNAs) are a diverse family of untranslated RNA molecules composed of less than 200 nucleotides (1,2). The most commonly studied small ncRNAs are microRNA (miRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), and transfer RNA (tRNA) (3). A growing number of small noncoding transcripts were identified to play important roles in gene regulation and RNA processing (4). Recent studies have shown that dysregulation of small ncRNAs has functional relevance in numerous human diseases, including cancer (5), neurological disorders, and cardiovascular diseases (6). Therefore, small ncRNAs may be of use in diagnosing and treating these disorders (7,8). Specifically, a plethora of research has been directed at the possible role of miRNA in the identification and diagnosis of various diseases. This chapter focuses on the involvement of miRNA in two prevalent pregnancy complications: gestational diabetes mellitus and preeclampsia.
Mobile DNA Sequences and Their Possible Role in Evolution
Published in S. K. Dutta, DNA Systematics, 2019
Georgii P. Georgiev, Yurii V. Ilyin, Alexei P. Ryskov, Tatiana I. Gerasimova
Another source of RNA for reverse transcription is small nuclear RNA (snRNA). Indeed, a number of pseudogenes were found for the genes responsible for the synthesis of snRNA, which are also known to be transcribed by RNA-polymerase II. Again, these pseudogenes are flanked by short direct repeats, i.e., represent the insertion sequences.109,110In several cases, the mechanism of reverse transcription seems to be very clear. For example, the pseudogenes of U12 and U3 RNAs are often truncated, lacking the 3′ end. It is known that U3 RNA possesses a secondary structure forming a hairpin involving its 3′ end. Therefore, its 3′ end may be used as a primer for reverse transcription of the 5′ part of the molecule not involved in hairpin formation. The borders of DNA synthesized in vitro by reverse transcriptase with a free U3 RNA template or with an RNP particle containing U3 RNA were exactly the same as the borders of U3 RNA pseudogenes.110a Thus, the conclusion about the involvement of reverse transcriptase in pseudogene insertion seems to be well proved.
rDNA: Evolution Over a Billion Years
Published in S. K. Dutta, DNA Systematics, 2019
The transcription initiation site is located 230 bp downstream of the VrDNA region209,210 and a fragment containing this site has been subcloned. Approximately 960 bp surrounding the site have been sequenced. A cluster of Τ residues is located upstream from transcription initiation, a 15 bp sequence occurs twice within a 100 nucleotide interval prior to this Τ residue cluster, and the RNA processing site is 650 bp from the transcription initiation site.211–213 Small nuclear RNA molecules (snP1 RNAs) have been shown to originate from the spacer preceding the initiation site,214 a situation somewhat analogous to that found in Xenopus (see Section II).
The discovery and development of RNA-based therapies for treatment of HIV-1 infection
Published in Expert Opinion on Drug Discovery, 2023
Michelle J Chen, Anne Gatignol, Robert J. Scarborough
U1 small nuclear RNA (U1 snRNA) interference (U1i) is a distinct gene silencing mechanism inspired by the naturally occurring eukaryotic U1 ribonucleoprotein complex that plays a role in precursor mRNA splicing [32,168]. The U1 small nuclear ribonucleoprotein (snRNP) complex consists of seven spliceosomal Smith (Sm) proteins, three U1-specific proteins, and the 164 nt U1 snRNA folded into a four stem-loop structure. This complex is important for defining the 5’ splice sites and regulating 3’-end processing on pre-mRNAs. By binding to cis-elements up- or down-stream of the polyadenylation site, U1 snRNPs can inhibit polyadenylation. Transcripts lacking the polyA tail are unstable and degraded by host cell machinery, thus preventing the maturation of pre-mRNAs. Molecular engineering of the U1 snRNA exploits this natural repression function to silence gene expression. The U1 snRNA is modified at its 5’ end to code for a ~10 nt sequence complementary to the target RNA [169]. The resulting synthetic U1i RNA is then cloned under the U1 promoter and expressed in the cell where it transits to the nucleus to recruit U1 snRNPs to the target RNA, resulting in sequence-specific post-transcriptional gene silencing (Figure 4A).
Identification of biomarkers for early diagnosis of multiple myeloma by weighted gene co-expression network analysis and their clinical relevance
Published in Hematology, 2022
Mengling Xu, Ye Meng, Qian Li, Alice Charwudzi, Hui Qin, Shudao Xiong
SnoRNAs are a group of regulatory RNAs that mainly reside in the nucleolus and post-transcriptionally modify ribosomal RNA (rRNA) and small nuclear RNA (snRNA), which are associated with malignancy by mediating gene expression and cancer signaling pathways [29]. Currently, more and more evidence shows that SNORNA also plays an important role in the regulation of oncogenesis and as a biomarker of cancers [30], including liver cancer [31], colorectal cancer (CRC) [32], but few studies focused on its mechanisms. However, to the best of our knowledge, to date, limited information is available on the expression and function of SNORNA in multiple myeloma. Because SNORNA is abundant and easily detectable in solid tumors and blood and may be functionally relevant in tumorigenesis, they could become a biomarker and major target for cancer therapy. In our study, the expression of SNORA71A in multiple myeloma was significantly higher and increased with disease progression and could be used as a new diagnostic marker for multiple myeloma. Our results suggest that we can assess patients’ condition by detecting the expression level of SNORA71A in peripheral blood, thereby reducing the pain and medical costs of bone marrow puncture in patients. However, its mechanism of action and clinical value need further exploration in lumber samples of multiple myeloma patients in the future.
Primary Immunodeficiency and Thrombocytopenia
Published in International Reviews of Immunology, 2022
Maryam Mohtashami, Azadehsadat Razavi, Hassan Abolhassani, Asghar Aghamohammadi, Reza Yazdani
Another syndrome is Microcephalic osteo-dysplastic primordial dwarfism type 1 (MOPD1). This deficiency is caused by mutations in the RNU4ATAC gene, which is responsible for encoding the small nuclear RNA (snRNA) U4atac [77].. Although the phenotype of Roifman syndrome and MOPD 1, called Taybi-Linder syndrome, are different from each other, both of them originate from a mutation in the RNU4ATAC gene. On the other side, megakaryopoiesis from peripheral blood-derived CD34+ hematopoietic stem cells (HSCs) in patients with Roifman syndrome are decreased under in vitro conditions, so it is deduced that platelet production reduced. Further supportive evidence has provided that despite the association of platelet with elevated tubulin, actin and alpha and dense granule, aggregation of platelets against agonists such as ATP has not increased. Besides, thrombocytopenia is a striking feature of MOPD1 deficiency [20, 46].