Limits...
The Three Paralogous MicroRNA Clusters in Development and Disease, miR-17-92, miR-106a-363, and miR-106b-25.

Khuu C, Utheim TP, Sehic A - Scientifica (Cairo) (2016)

Bottom Line: As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions.Further understanding of these three clusters and their functions will increase our knowledge about cancer progression.The present review discusses the characteristics and functions of these three miRNA clusters.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway.

ABSTRACT
MicroRNAs (miRNAs) form a class of noncoding RNA genes whose products are small single-stranded RNAs that are involved in the regulation of translation and degradation of mRNAs. There is a fine balance between deregulation of normal developmental programs and tumor genesis. An increasing body of evidence suggests that altered expression of miRNAs is entailed in the pathogenesis of human cancers. Studies in mouse and human cells have identified the miR-17-92 cluster as a potential oncogene. The miR-17-92 cluster is often amplified or overexpressed in human cancers and has recently emerged as the prototypical oncogenic polycistron miRNA. The functional analysis of miR-17-92 is intricate by the existence of two paralogues: miR-106a-363 and miR-106b-25. During early evolution of vertebrates, it is likely that the three clusters commenced via a series of duplication and deletion occurrences. As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions. Further understanding of these three clusters and their functions will increase our knowledge about cancer progression. The present review discusses the characteristics and functions of these three miRNA clusters.

No MeSH data available.


Related in: MedlinePlus

Biogenesis and mechanism of action of miRNAs. (a) miRNAs are transcribed mainly by polymerase II (A) from a gene encoding a single miRNA (B), or from a polycistronic gene (C), or from a gene in an intronic region (D). Resulting pri-miRNAs are processed by type III RNase Drosha. The newly formed stem-loop structure, pre-miRNA, is recognized by the XPO5, RanGTP complex, and is transported to the cytoplasm by exportin-5 (E). Dicer cleaves the loop (F), leaving a double-stranded fragment, the miRNA-3p:miRNA-5p duplex (G). The duplex is then unwound and loaded into the miRISC complex (H) where it recognizes and anneals to the UTR of mRNA target (I). The messenger RNA:miRISC complex mediates translational repression (J) or mRNA decay (K). (b) Processing of a pre-miRNA gives rise to two mature miRNAs named miR-XXX-3p and miR-XXX-5p where miR-XXX-3p miRNA originates from 3′-end and miR-XXX-5p miRNA originates from 5′-end of the pre-miRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4834410&req=5

fig1: Biogenesis and mechanism of action of miRNAs. (a) miRNAs are transcribed mainly by polymerase II (A) from a gene encoding a single miRNA (B), or from a polycistronic gene (C), or from a gene in an intronic region (D). Resulting pri-miRNAs are processed by type III RNase Drosha. The newly formed stem-loop structure, pre-miRNA, is recognized by the XPO5, RanGTP complex, and is transported to the cytoplasm by exportin-5 (E). Dicer cleaves the loop (F), leaving a double-stranded fragment, the miRNA-3p:miRNA-5p duplex (G). The duplex is then unwound and loaded into the miRISC complex (H) where it recognizes and anneals to the UTR of mRNA target (I). The messenger RNA:miRISC complex mediates translational repression (J) or mRNA decay (K). (b) Processing of a pre-miRNA gives rise to two mature miRNAs named miR-XXX-3p and miR-XXX-5p where miR-XXX-3p miRNA originates from 3′-end and miR-XXX-5p miRNA originates from 5′-end of the pre-miRNA.

Mentions: MicroRNAs encoding genes are located both in intronic and in exonic regions of the genome. The processing of a pre-miRNA into mature miRNAs results in two 19–23 nt long miRNAs named miR-XXX-5p and miR-XXX-3p; the mature miR-XXX-5p miRNA originates from 5′-end and miR-XXX-3p originates from 3′-end of the pre-miRNA (Figure 1). MicroRNAs may be transcribed from individual genes or as clusters [9]. Approximately 30% of miRNAs are transcribed as polycistronic clusters [10–12]. Transcription may be regulated either by its own promoter or by a host gene promoter [13]. A cluster of miRNAs is defined as several miRNA genes located adjacent to each other on the chromosome, which are transcribed as one long pri-miRNA transcript and subsequently processed into the individual pre-miRNAs [14]. The genomic organization of miRNAs in a cluster may function to protect it from degradation as the secondary structure of a longer pri-miRNA is complex with numerous hairpins that stabilize the RNA [15]. This arrangement may have particular significance as regards regulation of gene expression. Clustered miRNAs with similar sequences may regulate a set of mRNA targets and therefore function as powerful regulators of specific cellular activities. MicroRNA clusters are often transcribed by a common promoter [16, 17] and range from <100 base pairs (bp) to 50 kilobases (kb) [14, 15]. MicroRNAs within a cluster are often, but not always, paralogous with high sequence homology. This suggests that microRNAs are the result of genomic duplications [18, 19]. High sequence homology between the miRNAs in a cluster classifies them as a family and permits both common and unique mRNA targets. These mRNA targets are often present within the same pathway, allowing these miRNAs to have regulatory influence over several components of a cellular process. Consistent with this role for miRNA clusters, several clusters have been found to be important for normal development and disease pathology [20–24].


The Three Paralogous MicroRNA Clusters in Development and Disease, miR-17-92, miR-106a-363, and miR-106b-25.

Khuu C, Utheim TP, Sehic A - Scientifica (Cairo) (2016)

Biogenesis and mechanism of action of miRNAs. (a) miRNAs are transcribed mainly by polymerase II (A) from a gene encoding a single miRNA (B), or from a polycistronic gene (C), or from a gene in an intronic region (D). Resulting pri-miRNAs are processed by type III RNase Drosha. The newly formed stem-loop structure, pre-miRNA, is recognized by the XPO5, RanGTP complex, and is transported to the cytoplasm by exportin-5 (E). Dicer cleaves the loop (F), leaving a double-stranded fragment, the miRNA-3p:miRNA-5p duplex (G). The duplex is then unwound and loaded into the miRISC complex (H) where it recognizes and anneals to the UTR of mRNA target (I). The messenger RNA:miRISC complex mediates translational repression (J) or mRNA decay (K). (b) Processing of a pre-miRNA gives rise to two mature miRNAs named miR-XXX-3p and miR-XXX-5p where miR-XXX-3p miRNA originates from 3′-end and miR-XXX-5p miRNA originates from 5′-end of the pre-miRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4834410&req=5

fig1: Biogenesis and mechanism of action of miRNAs. (a) miRNAs are transcribed mainly by polymerase II (A) from a gene encoding a single miRNA (B), or from a polycistronic gene (C), or from a gene in an intronic region (D). Resulting pri-miRNAs are processed by type III RNase Drosha. The newly formed stem-loop structure, pre-miRNA, is recognized by the XPO5, RanGTP complex, and is transported to the cytoplasm by exportin-5 (E). Dicer cleaves the loop (F), leaving a double-stranded fragment, the miRNA-3p:miRNA-5p duplex (G). The duplex is then unwound and loaded into the miRISC complex (H) where it recognizes and anneals to the UTR of mRNA target (I). The messenger RNA:miRISC complex mediates translational repression (J) or mRNA decay (K). (b) Processing of a pre-miRNA gives rise to two mature miRNAs named miR-XXX-3p and miR-XXX-5p where miR-XXX-3p miRNA originates from 3′-end and miR-XXX-5p miRNA originates from 5′-end of the pre-miRNA.
Mentions: MicroRNAs encoding genes are located both in intronic and in exonic regions of the genome. The processing of a pre-miRNA into mature miRNAs results in two 19–23 nt long miRNAs named miR-XXX-5p and miR-XXX-3p; the mature miR-XXX-5p miRNA originates from 5′-end and miR-XXX-3p originates from 3′-end of the pre-miRNA (Figure 1). MicroRNAs may be transcribed from individual genes or as clusters [9]. Approximately 30% of miRNAs are transcribed as polycistronic clusters [10–12]. Transcription may be regulated either by its own promoter or by a host gene promoter [13]. A cluster of miRNAs is defined as several miRNA genes located adjacent to each other on the chromosome, which are transcribed as one long pri-miRNA transcript and subsequently processed into the individual pre-miRNAs [14]. The genomic organization of miRNAs in a cluster may function to protect it from degradation as the secondary structure of a longer pri-miRNA is complex with numerous hairpins that stabilize the RNA [15]. This arrangement may have particular significance as regards regulation of gene expression. Clustered miRNAs with similar sequences may regulate a set of mRNA targets and therefore function as powerful regulators of specific cellular activities. MicroRNA clusters are often transcribed by a common promoter [16, 17] and range from <100 base pairs (bp) to 50 kilobases (kb) [14, 15]. MicroRNAs within a cluster are often, but not always, paralogous with high sequence homology. This suggests that microRNAs are the result of genomic duplications [18, 19]. High sequence homology between the miRNAs in a cluster classifies them as a family and permits both common and unique mRNA targets. These mRNA targets are often present within the same pathway, allowing these miRNAs to have regulatory influence over several components of a cellular process. Consistent with this role for miRNA clusters, several clusters have been found to be important for normal development and disease pathology [20–24].

Bottom Line: As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions.Further understanding of these three clusters and their functions will increase our knowledge about cancer progression.The present review discusses the characteristics and functions of these three miRNA clusters.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway.

ABSTRACT
MicroRNAs (miRNAs) form a class of noncoding RNA genes whose products are small single-stranded RNAs that are involved in the regulation of translation and degradation of mRNAs. There is a fine balance between deregulation of normal developmental programs and tumor genesis. An increasing body of evidence suggests that altered expression of miRNAs is entailed in the pathogenesis of human cancers. Studies in mouse and human cells have identified the miR-17-92 cluster as a potential oncogene. The miR-17-92 cluster is often amplified or overexpressed in human cancers and has recently emerged as the prototypical oncogenic polycistron miRNA. The functional analysis of miR-17-92 is intricate by the existence of two paralogues: miR-106a-363 and miR-106b-25. During early evolution of vertebrates, it is likely that the three clusters commenced via a series of duplication and deletion occurrences. As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions. Further understanding of these three clusters and their functions will increase our knowledge about cancer progression. The present review discusses the characteristics and functions of these three miRNA clusters.

No MeSH data available.


Related in: MedlinePlus