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Decoding ARE-mediated decay: is microRNA part of the equation?

von Roretz C, Gallouzi IE - J. Cell Biol. (2008)

Bottom Line: Messenger ribonucleic acids (mRNAs) containing adenine/uridine-rich elements (AREs) in their 3' untranslated region are particularly labile, allowing for the regulation of expression for growth factors, oncoproteins, and cytokines.The regulators, effectors, and location of ARE-mediated decay (AMD) have been investigated by many groups in recent years, and several links have been found between AMD and microRNA-mediated decay.We highlight these similarities, along with recent advances in the field of AMD, and also mention how there is still much left unknown surrounding this specialized mode of mRNA decay.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Department, McGill University, Montreal, Canada.

ABSTRACT
Messenger ribonucleic acids (mRNAs) containing adenine/uridine-rich elements (AREs) in their 3' untranslated region are particularly labile, allowing for the regulation of expression for growth factors, oncoproteins, and cytokines. The regulators, effectors, and location of ARE-mediated decay (AMD) have been investigated by many groups in recent years, and several links have been found between AMD and microRNA-mediated decay. We highlight these similarities, along with recent advances in the field of AMD, and also mention how there is still much left unknown surrounding this specialized mode of mRNA decay.

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Related in: MedlinePlus

Model for AMD. Based on current literature, we propose three major pathways by which AMD is executed. In the first, AUBPs promoting degradation (e.g. TTP) may bind the ARE of the target mRNA and help recruit decapping enzymes such as Dcp1/2. After decapping, the 5′ to 3′ exoribonuclease Xrn1 may then carry out 5′ to 3′ decay. In the second, AUBPs may recruit endoribonucleases to internally cleave the target mRNA. Some data implicate miRNAs in this AUBP interaction, such as the miR16–AGO2–TTP complex (Jing et al., 2005). In the third, AUBPs may recruit deadenylases (such as PARN or CCR4) to remove the poly (A) tail from the 3′ terminus of the mRNA, and 3′ to 5′ degradation may then occur by way of the exosome. miRNP complexes may also be involved in recruiting the machineries for this pathway. Stabilizing AUBPs, such as HuR, may be implicated in one or more of these pathways by competing with binding of destabilizing AUBPs or by preventing miRNA–mRNA interactions.
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fig1: Model for AMD. Based on current literature, we propose three major pathways by which AMD is executed. In the first, AUBPs promoting degradation (e.g. TTP) may bind the ARE of the target mRNA and help recruit decapping enzymes such as Dcp1/2. After decapping, the 5′ to 3′ exoribonuclease Xrn1 may then carry out 5′ to 3′ decay. In the second, AUBPs may recruit endoribonucleases to internally cleave the target mRNA. Some data implicate miRNAs in this AUBP interaction, such as the miR16–AGO2–TTP complex (Jing et al., 2005). In the third, AUBPs may recruit deadenylases (such as PARN or CCR4) to remove the poly (A) tail from the 3′ terminus of the mRNA, and 3′ to 5′ degradation may then occur by way of the exosome. miRNP complexes may also be involved in recruiting the machineries for this pathway. Stabilizing AUBPs, such as HuR, may be implicated in one or more of these pathways by competing with binding of destabilizing AUBPs or by preventing miRNA–mRNA interactions.

Mentions: Recent studies have demonstrated that in some cases, 5′ to 3′ mRNA decay is also significant (Stoecklin et al., 2006). The major player responsible for this nonexosomal ribonuclease activity is Xrn1 (Larimer and Stevens, 1990). Intriguingly, both Xrn1 and PM-Scl-75 have been shown to be essential for adequate AMD (Yang et al., 2004a; Stoecklin et al., 2006), suggesting that more than one pathway is being used by this process (Fig. 1). Regardless of the direction exonuclease cleavage occurs in, other factors, such as decapping enzymes and deadenylases, are also typically implicated, and these have also been shown to associate with AUBPs (Table I). Evidence has also pointed toward endonucleases being involved in cleaving ARE mRNA. GAP-SH3 binding protein and the erythroid cell–enriched endoribonuclease have actually been shown to target the 3′ untranslated regions of ARE mRNA (Wang and Kiledjian, 2000; Tourriere et al., 2001; Schoenberg, 2007), making them possible suspects in AMD .


Decoding ARE-mediated decay: is microRNA part of the equation?

von Roretz C, Gallouzi IE - J. Cell Biol. (2008)

Model for AMD. Based on current literature, we propose three major pathways by which AMD is executed. In the first, AUBPs promoting degradation (e.g. TTP) may bind the ARE of the target mRNA and help recruit decapping enzymes such as Dcp1/2. After decapping, the 5′ to 3′ exoribonuclease Xrn1 may then carry out 5′ to 3′ decay. In the second, AUBPs may recruit endoribonucleases to internally cleave the target mRNA. Some data implicate miRNAs in this AUBP interaction, such as the miR16–AGO2–TTP complex (Jing et al., 2005). In the third, AUBPs may recruit deadenylases (such as PARN or CCR4) to remove the poly (A) tail from the 3′ terminus of the mRNA, and 3′ to 5′ degradation may then occur by way of the exosome. miRNP complexes may also be involved in recruiting the machineries for this pathway. Stabilizing AUBPs, such as HuR, may be implicated in one or more of these pathways by competing with binding of destabilizing AUBPs or by preventing miRNA–mRNA interactions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2315667&req=5

fig1: Model for AMD. Based on current literature, we propose three major pathways by which AMD is executed. In the first, AUBPs promoting degradation (e.g. TTP) may bind the ARE of the target mRNA and help recruit decapping enzymes such as Dcp1/2. After decapping, the 5′ to 3′ exoribonuclease Xrn1 may then carry out 5′ to 3′ decay. In the second, AUBPs may recruit endoribonucleases to internally cleave the target mRNA. Some data implicate miRNAs in this AUBP interaction, such as the miR16–AGO2–TTP complex (Jing et al., 2005). In the third, AUBPs may recruit deadenylases (such as PARN or CCR4) to remove the poly (A) tail from the 3′ terminus of the mRNA, and 3′ to 5′ degradation may then occur by way of the exosome. miRNP complexes may also be involved in recruiting the machineries for this pathway. Stabilizing AUBPs, such as HuR, may be implicated in one or more of these pathways by competing with binding of destabilizing AUBPs or by preventing miRNA–mRNA interactions.
Mentions: Recent studies have demonstrated that in some cases, 5′ to 3′ mRNA decay is also significant (Stoecklin et al., 2006). The major player responsible for this nonexosomal ribonuclease activity is Xrn1 (Larimer and Stevens, 1990). Intriguingly, both Xrn1 and PM-Scl-75 have been shown to be essential for adequate AMD (Yang et al., 2004a; Stoecklin et al., 2006), suggesting that more than one pathway is being used by this process (Fig. 1). Regardless of the direction exonuclease cleavage occurs in, other factors, such as decapping enzymes and deadenylases, are also typically implicated, and these have also been shown to associate with AUBPs (Table I). Evidence has also pointed toward endonucleases being involved in cleaving ARE mRNA. GAP-SH3 binding protein and the erythroid cell–enriched endoribonuclease have actually been shown to target the 3′ untranslated regions of ARE mRNA (Wang and Kiledjian, 2000; Tourriere et al., 2001; Schoenberg, 2007), making them possible suspects in AMD .

Bottom Line: Messenger ribonucleic acids (mRNAs) containing adenine/uridine-rich elements (AREs) in their 3' untranslated region are particularly labile, allowing for the regulation of expression for growth factors, oncoproteins, and cytokines.The regulators, effectors, and location of ARE-mediated decay (AMD) have been investigated by many groups in recent years, and several links have been found between AMD and microRNA-mediated decay.We highlight these similarities, along with recent advances in the field of AMD, and also mention how there is still much left unknown surrounding this specialized mode of mRNA decay.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Department, McGill University, Montreal, Canada.

ABSTRACT
Messenger ribonucleic acids (mRNAs) containing adenine/uridine-rich elements (AREs) in their 3' untranslated region are particularly labile, allowing for the regulation of expression for growth factors, oncoproteins, and cytokines. The regulators, effectors, and location of ARE-mediated decay (AMD) have been investigated by many groups in recent years, and several links have been found between AMD and microRNA-mediated decay. We highlight these similarities, along with recent advances in the field of AMD, and also mention how there is still much left unknown surrounding this specialized mode of mRNA decay.

Show MeSH
Related in: MedlinePlus