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Dysregulation of microRNA expression and function contributes to the etiology of fetal alcohol spectrum disorders.

Balaraman S, Tingling JD, Tsai PC, Miranda RC - Alcohol Res (2013)

Bottom Line: MicroRNAs (miRNAs) are members of a large class of non-protein-coding RNA (ncRNA) molecules that represent a significant, but until recently unappreciated, layer of cellular regulation.A small but rapidly expanding body of studies using a variety of animal- and cell culture-based experimental models also has shown that miRNAs are important targets of alcohol during fetal development and that their dysregulation likely plays a significant role in the etiology of fetal alcohol spectrum disorders (FASD).Accordingly, an analysis of the regulation and function of these miRNAs may yield important clues to the management of FASD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, Texas, USA.

ABSTRACT
MicroRNAs (miRNAs) are members of a large class of non-protein-coding RNA (ncRNA) molecules that represent a significant, but until recently unappreciated, layer of cellular regulation. Assessment of the generation and function of miRNAs suggests that these ncRNAs are vulnerable to interference from genetic, epigenetic, and environmental factors. A small but rapidly expanding body of studies using a variety of animal- and cell culture-based experimental models also has shown that miRNAs are important targets of alcohol during fetal development and that their dysregulation likely plays a significant role in the etiology of fetal alcohol spectrum disorders (FASD). Accordingly, an analysis of the regulation and function of these miRNAs may yield important clues to the management of FASD.

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Related in: MedlinePlus

Models for standard (i.e., canonical) and disturbed (i.e., noncanonical) modes of miRNA biogenesis and function. (A) miRNAs often are generated (i.e., transcribed) from miRNA genes, as long mRNA-like transcripts, with a “cap” at the start (i.e., 5′-end) and several adenosine units at the end (i.e., 3′- polyA tail). The initial primary miRNA transcripts (pri-miRNAs) are processed to shorter, hairpin-shaped premature miRNAs (pre-miRNAs) by a protein complex called the DiGeorge syndrome critical region-8 (Drosha/DGCR8) complex. The pre-miRNAs then are transported to the cytoplasm for final processing into mature miRNAs by the Dicer complex. Mature miRNAs attain their function by being integrated into RNA-induced silencing complexes (RISC) that can degrade target mRNAs or silence translation. Processed miRNAs also can relocate to the nucleus to influence chromatin remodeling. (B) Disturbances in Drosha/DGCR8 processing (e.g., because of a mutation in the genes encoding these enzymes) may reveal alternate, mRNA-like functions of unprocessed pri-miRNAs and result in disrupted stem cell maturation.
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f1-arcr-35-1-18: Models for standard (i.e., canonical) and disturbed (i.e., noncanonical) modes of miRNA biogenesis and function. (A) miRNAs often are generated (i.e., transcribed) from miRNA genes, as long mRNA-like transcripts, with a “cap” at the start (i.e., 5′-end) and several adenosine units at the end (i.e., 3′- polyA tail). The initial primary miRNA transcripts (pri-miRNAs) are processed to shorter, hairpin-shaped premature miRNAs (pre-miRNAs) by a protein complex called the DiGeorge syndrome critical region-8 (Drosha/DGCR8) complex. The pre-miRNAs then are transported to the cytoplasm for final processing into mature miRNAs by the Dicer complex. Mature miRNAs attain their function by being integrated into RNA-induced silencing complexes (RISC) that can degrade target mRNAs or silence translation. Processed miRNAs also can relocate to the nucleus to influence chromatin remodeling. (B) Disturbances in Drosha/DGCR8 processing (e.g., because of a mutation in the genes encoding these enzymes) may reveal alternate, mRNA-like functions of unprocessed pri-miRNAs and result in disrupted stem cell maturation.

Mentions: miRNAs are encoded within the genome either as independent genes or in gene clusters; however, they also can be encoded within introns1 of protein-coding genes, or even within introns and exons of another type of ncRNA called long intergenic non-(protein)-coding RNAs (lincRNAs). The generation of mature miRNAs from these coding sequences is a multistep process, as follows (see figure 1A):


Dysregulation of microRNA expression and function contributes to the etiology of fetal alcohol spectrum disorders.

Balaraman S, Tingling JD, Tsai PC, Miranda RC - Alcohol Res (2013)

Models for standard (i.e., canonical) and disturbed (i.e., noncanonical) modes of miRNA biogenesis and function. (A) miRNAs often are generated (i.e., transcribed) from miRNA genes, as long mRNA-like transcripts, with a “cap” at the start (i.e., 5′-end) and several adenosine units at the end (i.e., 3′- polyA tail). The initial primary miRNA transcripts (pri-miRNAs) are processed to shorter, hairpin-shaped premature miRNAs (pre-miRNAs) by a protein complex called the DiGeorge syndrome critical region-8 (Drosha/DGCR8) complex. The pre-miRNAs then are transported to the cytoplasm for final processing into mature miRNAs by the Dicer complex. Mature miRNAs attain their function by being integrated into RNA-induced silencing complexes (RISC) that can degrade target mRNAs or silence translation. Processed miRNAs also can relocate to the nucleus to influence chromatin remodeling. (B) Disturbances in Drosha/DGCR8 processing (e.g., because of a mutation in the genes encoding these enzymes) may reveal alternate, mRNA-like functions of unprocessed pri-miRNAs and result in disrupted stem cell maturation.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860419&req=5

f1-arcr-35-1-18: Models for standard (i.e., canonical) and disturbed (i.e., noncanonical) modes of miRNA biogenesis and function. (A) miRNAs often are generated (i.e., transcribed) from miRNA genes, as long mRNA-like transcripts, with a “cap” at the start (i.e., 5′-end) and several adenosine units at the end (i.e., 3′- polyA tail). The initial primary miRNA transcripts (pri-miRNAs) are processed to shorter, hairpin-shaped premature miRNAs (pre-miRNAs) by a protein complex called the DiGeorge syndrome critical region-8 (Drosha/DGCR8) complex. The pre-miRNAs then are transported to the cytoplasm for final processing into mature miRNAs by the Dicer complex. Mature miRNAs attain their function by being integrated into RNA-induced silencing complexes (RISC) that can degrade target mRNAs or silence translation. Processed miRNAs also can relocate to the nucleus to influence chromatin remodeling. (B) Disturbances in Drosha/DGCR8 processing (e.g., because of a mutation in the genes encoding these enzymes) may reveal alternate, mRNA-like functions of unprocessed pri-miRNAs and result in disrupted stem cell maturation.
Mentions: miRNAs are encoded within the genome either as independent genes or in gene clusters; however, they also can be encoded within introns1 of protein-coding genes, or even within introns and exons of another type of ncRNA called long intergenic non-(protein)-coding RNAs (lincRNAs). The generation of mature miRNAs from these coding sequences is a multistep process, as follows (see figure 1A):

Bottom Line: MicroRNAs (miRNAs) are members of a large class of non-protein-coding RNA (ncRNA) molecules that represent a significant, but until recently unappreciated, layer of cellular regulation.A small but rapidly expanding body of studies using a variety of animal- and cell culture-based experimental models also has shown that miRNAs are important targets of alcohol during fetal development and that their dysregulation likely plays a significant role in the etiology of fetal alcohol spectrum disorders (FASD).Accordingly, an analysis of the regulation and function of these miRNAs may yield important clues to the management of FASD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, Texas, USA.

ABSTRACT
MicroRNAs (miRNAs) are members of a large class of non-protein-coding RNA (ncRNA) molecules that represent a significant, but until recently unappreciated, layer of cellular regulation. Assessment of the generation and function of miRNAs suggests that these ncRNAs are vulnerable to interference from genetic, epigenetic, and environmental factors. A small but rapidly expanding body of studies using a variety of animal- and cell culture-based experimental models also has shown that miRNAs are important targets of alcohol during fetal development and that their dysregulation likely plays a significant role in the etiology of fetal alcohol spectrum disorders (FASD). Accordingly, an analysis of the regulation and function of these miRNAs may yield important clues to the management of FASD.

Show MeSH
Related in: MedlinePlus