With the introduction of next generation sequencing methods, such as RNA

With the introduction of next generation sequencing methods, such as RNA sequencing, it has become apparent that alterations in the non-coding regions of our genome are important in the development of cancer. include V(D)J recombination, quick proliferation, somatic hypermutation and clonal selection, posing a risk of malignant transformation at each step. The aim of this review is usually to provide insight into how lncRNAs including circRNAs, participate in normal B-cell differentiation, and how deregulation of these molecules is usually involved in the development of B-cell malignancies. We describe the prognostic value and functional significance of specific deregulated lncRNAs in diseases such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma and multiple myeloma, and we provide an overview of the current knowledge around the role of circRNAs in these diseases. regulate gene expression by serving as a scaffold for histone modification enzymes [11], and can serve as a transcriptional coactivator or repressor [12,13]. participates in nuclear retention of mRNAs [14], and is involved in alternate splicing [15]. In the cytoplasm, lncRNAs can act as decoys, inhibiting protein synthesis of host genes [16], or regulating the translation of specific transcripts, which has been shown for [17]. Observe Figure 2. Open in a separate window Physique 2 Cellular functions SGX-523 ic50 of lncRNAs. (a) LncRNAs as scaffolds for histone modification enzymes. (or in as a coactivator for p53-dependent transcription of p21, or in by interacting with heterogenous nuclear ribonucleoprotein K (hnRNP-K) to mediate repression of distant p53 target genes (c) LncRNAs such as can retain mRNAs in the nucleus by associating with paraspeckle proteins such as PSF, PSP1, and p54. (d) In tissue-specific option splicing, lncRNAs participate by recruiting serine/arginine splicing factors (SR) to nuclear speckles, and thereby to the target pre-mRNAs, as KIFC1 shown for interacts with translation initiation factor eIF4E to suppress the translation of c-myc mRNA. A newly recognised subclass of lncRNA, named circular RNA (circRNA), have emerged as important gene regulatory molecules. CircRNAs are created through a backsplicing event, which covalently link the 3 end of an exon to the 5 end of the same or an upstream exon. Most circRNAs originate from a host gene, and their biogenesis is usually facilitated either by flanking homologous inverted repeats bringing the splice sites in close proximity, or by dimerization of RNA binding proteins [18,19]. These molecules also display tissue- and disease-specific expression patterns, but, unlike other lncRNAs, many circRNAs SGX-523 ic50 are highly evolutionary conserved [18,20]. Due to the lack of free ends, circRNAs are highly stable molecules that are resistant to exonucleases [18], and thus they hold great potential as diagnostic and prognostic biomarkers. It has been shown that particular circRNAs function as direct or indirect regulators of host gene expression at the transcriptional level [21,22], as sponges of microRNAs SGX-523 ic50 (miRNAs) [23,24], as protein scaffolds [25], or as specific or global regulators of protein translation [26,27]. SGX-523 ic50 Recent studies have reported that some circRNAs under certain circumstances can serve as templates for translation [28,29,30,31], yet the vast majority of circRNAs are considered to be non-coding [32]. See Figure 3. Open in a separate window Figure 3 Proposed functions of circular RNAs (circRNAs). (a) CircRNAs can regulate gene expression indirectly through competition with canonical splicing. (b) Exon-intron circular RNAs (EICircRNAs) can directly enhance the transcription of host genes through interaction with the transcription complex. (c) CircRNAs can function as microRNA (miRNA) sponges, here exemplified by circular sponge for miR-7 (ciRS-7), which has 70 binding sites for miR-7. In the presence of ciRS-7, SGX-523 ic50 miR-7 target mRNA will be released from the miRNA-mediated repression. Upon binding of miR-671, an argonaute 2 (AGO2)-mediated cleavage occurs, providing immediate activation of miR-7 (d) CircRNAs can function as protein scaffolds or decoys. CircFOXO3 forms a ternary complex with p21 and cyclin-dependent kinase 2 (CDK2), blocking the interaction with cyclin A and cyclin E, thereby retarding cell cycle entry. (e) CircRNAs can serve as specific or global regulators of protein translation. CircRNA polyadenylate-binding protein nuclear (PABPN) sequesters the RNA-binding protein Hu Antigen R (HuR), leading to decreased PABPN mRNA translation. (f) Under certain circumstances, circRNAs have been reported to be translated. Several studies have shown that lncRNAs and circRNAs are involved in cell differentiation and tissue development [33,34,35,36], and they are central players in.

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