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Small and Long Regulatory RNAs in the Immune System and Immune Diseases.

Stachurska A, Zorro MM, van der Sijde MR, Withoff S - Front Immunol (2014)

Bottom Line: Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors.However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs) have given enormous momentum to a whole new field of biology: the regulatory RNAs.In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.

ABSTRACT
Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs) have given enormous momentum to a whole new field of biology: the regulatory RNAs. In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems. Finally, we describe what is known about the involvement of micro-RNAs and lncRNAs in three different autoimmune diseases (celiac disease, inflammatory bowel disease, and multiple sclerosis).

No MeSH data available.


Related in: MedlinePlus

Multiple layers of gene expression controlled by transcription factors, miRNAs, and lncRNAs. (A) Protein-coding genes are transcribed into mRNA, which subsequently are translated into proteins. These proteins can function as the classical transcription factors. (B) There is a second class of RNAs that is not translated into protein but rather is regulating the expression of other transcripts. The third class of transcripts described in this review (C) is the long non-coding RNAs that can regulate gene expression as well, although other functions for these transcripts have been described (see Figure 3). It is becoming clear that there is interaction within each class, but also between these three classes, which can converge on transcriptional outcome (see text for details).
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Figure 1: Multiple layers of gene expression controlled by transcription factors, miRNAs, and lncRNAs. (A) Protein-coding genes are transcribed into mRNA, which subsequently are translated into proteins. These proteins can function as the classical transcription factors. (B) There is a second class of RNAs that is not translated into protein but rather is regulating the expression of other transcripts. The third class of transcripts described in this review (C) is the long non-coding RNAs that can regulate gene expression as well, although other functions for these transcripts have been described (see Figure 3). It is becoming clear that there is interaction within each class, but also between these three classes, which can converge on transcriptional outcome (see text for details).

Mentions: The discovery of the first micro-RNA (miRNA) in 1993 (1, 2) was the start of research that has led to the understanding that gene regulation is not only controlled by proteins (transcription factors) but also RNA molecules. Since then, thousands of novel non-coding RNAs, which can be subdivided into dozens of families (3), have been identified. Two of the most widely studied classes of non-coding RNAs, miRNAs and long non-coding RNAs (lncRNAs), are now recognized as important regulators of gene expression. These molecules are also designated as (small or long) regulatory RNAs. At the time of writing this review, the authorative miRNA database miRBase (release 21) describes 1,881 human miRNA precursors and 2,588 human mature miRNA sequences (4), whereas the GENCODE compendium (V19) mentions 13,870 human lncRNA genes (5). MiRNAs are thought to affect gene expression by inhibiting target mRNA translation (which leads indirectly to degradation of the target) or they can directly induce target mRNA degradation. Many lncRNAs are thought to be involved in chromatin modification processes that, in turn, affect gene expression levels (Figure 1). The role of miRNAs in homeostasis and the deregulation of miRNAs in human disease have been well established, but the role of lncRNAs in these processes is not yet fully appreciated. Here, we will review what is known about the role of miRNAs and lncRNAs in the development and activation of the adaptive and innate immune systems in health and disease.


Small and Long Regulatory RNAs in the Immune System and Immune Diseases.

Stachurska A, Zorro MM, van der Sijde MR, Withoff S - Front Immunol (2014)

Multiple layers of gene expression controlled by transcription factors, miRNAs, and lncRNAs. (A) Protein-coding genes are transcribed into mRNA, which subsequently are translated into proteins. These proteins can function as the classical transcription factors. (B) There is a second class of RNAs that is not translated into protein but rather is regulating the expression of other transcripts. The third class of transcripts described in this review (C) is the long non-coding RNAs that can regulate gene expression as well, although other functions for these transcripts have been described (see Figure 3). It is becoming clear that there is interaction within each class, but also between these three classes, which can converge on transcriptional outcome (see text for details).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202709&req=5

Figure 1: Multiple layers of gene expression controlled by transcription factors, miRNAs, and lncRNAs. (A) Protein-coding genes are transcribed into mRNA, which subsequently are translated into proteins. These proteins can function as the classical transcription factors. (B) There is a second class of RNAs that is not translated into protein but rather is regulating the expression of other transcripts. The third class of transcripts described in this review (C) is the long non-coding RNAs that can regulate gene expression as well, although other functions for these transcripts have been described (see Figure 3). It is becoming clear that there is interaction within each class, but also between these three classes, which can converge on transcriptional outcome (see text for details).
Mentions: The discovery of the first micro-RNA (miRNA) in 1993 (1, 2) was the start of research that has led to the understanding that gene regulation is not only controlled by proteins (transcription factors) but also RNA molecules. Since then, thousands of novel non-coding RNAs, which can be subdivided into dozens of families (3), have been identified. Two of the most widely studied classes of non-coding RNAs, miRNAs and long non-coding RNAs (lncRNAs), are now recognized as important regulators of gene expression. These molecules are also designated as (small or long) regulatory RNAs. At the time of writing this review, the authorative miRNA database miRBase (release 21) describes 1,881 human miRNA precursors and 2,588 human mature miRNA sequences (4), whereas the GENCODE compendium (V19) mentions 13,870 human lncRNA genes (5). MiRNAs are thought to affect gene expression by inhibiting target mRNA translation (which leads indirectly to degradation of the target) or they can directly induce target mRNA degradation. Many lncRNAs are thought to be involved in chromatin modification processes that, in turn, affect gene expression levels (Figure 1). The role of miRNAs in homeostasis and the deregulation of miRNAs in human disease have been well established, but the role of lncRNAs in these processes is not yet fully appreciated. Here, we will review what is known about the role of miRNAs and lncRNAs in the development and activation of the adaptive and innate immune systems in health and disease.

Bottom Line: Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors.However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs) have given enormous momentum to a whole new field of biology: the regulatory RNAs.In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.

ABSTRACT
Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs) have given enormous momentum to a whole new field of biology: the regulatory RNAs. In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems. Finally, we describe what is known about the involvement of micro-RNAs and lncRNAs in three different autoimmune diseases (celiac disease, inflammatory bowel disease, and multiple sclerosis).

No MeSH data available.


Related in: MedlinePlus