Limits...
Polyuridylation in Eukaryotes: A 3'-End Modification Regulating RNA Life.

Munoz-Tello P, Rajappa L, Coquille S, Thore S - Biomed Res Int (2015)

Bottom Line: Numerous types of modifications have been characterized, which are generally specific for a given type of RNA such as the CCA addition found in tRNAs.In recent years, the addition of nontemplated uridine nucleotides or uridylation has been shown to occur in various types of RNA molecules and in various cellular compartments with significantly different outcomes.The present review aims at summarizing the current knowledge on the various processes leading to RNA 3'-end uridylation and on their potential impacts in various diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Geneva, 1211 Geneva, Switzerland ; Department of Molecular Therapeutics, The Scripps Research Institute, 110 Scripps Way, Building A Room A265, Jupiter, FL 33458, USA.

ABSTRACT
In eukaryotes, mRNA polyadenylation is a well-known modification that is essential for many aspects of the protein-coding RNAs life cycle. However, modification of the 3' terminal nucleotide within various RNA molecules is a general and conserved process that broadly modulates RNA function in all kingdoms of life. Numerous types of modifications have been characterized, which are generally specific for a given type of RNA such as the CCA addition found in tRNAs. In recent years, the addition of nontemplated uridine nucleotides or uridylation has been shown to occur in various types of RNA molecules and in various cellular compartments with significantly different outcomes. Indeed, uridylation is able to alter RNA half-life both in positive and in negative ways, highlighting the importance of the enzymes in charge of performing this modification. The present review aims at summarizing the current knowledge on the various processes leading to RNA 3'-end uridylation and on their potential impacts in various diseases.

No MeSH data available.


Known functions of polyuridylation in the nucleus and in the mitochondria. (a) Functions in the nucleus. U6 snRNA is the only known substrate for polyuridylation in the nucleus by U6 TUTase. Polyuridylation is thought to regenerate the 3′-end of U6 snRNA following its shortening by exonucleases. If this RNA is adenylated, the polyuridylation event is inhibited and the U6 snRNA is degraded. If the RNA is polyuridylated, mature U6 snRNA is produced and incorporated in the splicing complex known as the spliceosome. (b) Function of polyuridylation in the mitochondria of trypanosomes. In order to be properly matured, gRNAs are polyuridylated by RET1 TUTase allowing the gRNA to “guide” the editing reaction. To be translationally competent, mitochondrial mRNAs require addition of a long A/U tail, which is performed by the RET1/KPAP1 complex and coordinated by the KPAF1/KPAF2 complex. The mRNA is then recognized by the ribosome and translation can be started.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4442281&req=5

fig2: Known functions of polyuridylation in the nucleus and in the mitochondria. (a) Functions in the nucleus. U6 snRNA is the only known substrate for polyuridylation in the nucleus by U6 TUTase. Polyuridylation is thought to regenerate the 3′-end of U6 snRNA following its shortening by exonucleases. If this RNA is adenylated, the polyuridylation event is inhibited and the U6 snRNA is degraded. If the RNA is polyuridylated, mature U6 snRNA is produced and incorporated in the splicing complex known as the spliceosome. (b) Function of polyuridylation in the mitochondria of trypanosomes. In order to be properly matured, gRNAs are polyuridylated by RET1 TUTase allowing the gRNA to “guide” the editing reaction. To be translationally competent, mitochondrial mRNAs require addition of a long A/U tail, which is performed by the RET1/KPAP1 complex and coordinated by the KPAF1/KPAF2 complex. The mRNA is then recognized by the ribosome and translation can be started.

Mentions: Until now, the only substrate of uridylation reported in the nucleus is the U6 snRNA (Figure 1). This RNA is uridylated by the U6 TUTase, which is an essential enzyme for cell survival in mammals [64]. SiRNA-mediated silencing of the U6 TUTase leads to U6 snRNA decay, confirming the necessity of uridylation for U6 snRNA stability [64]. U6 TUTase is responsible for the addition or restoration of at least four uridine residues at the 3′-end of U6 snRNA since 3′-end of U6 snRNA is constantly subjected to exonucleases activity [64, 76]. These four U residues form an intramolecular double strand with a stretch of adenines within the U6 snRNA molecule, which is important for mRNA splicing [64]. This uridylation event specifically in the nucleus allows the proper production of a splicing-competent U6 snRNP (Figure 2(a)). Mammalian U6 snRNA uridylation in vivo has been reported with up to 20 nucleotides added at the 3′-end of the RNA molecule [77, 78]. It is important to note that U6 snRNA is also subjected to adenylation and this event inhibits its uridylation (Figure 2(a)) [79]. Moreover, the 3′-end of U6 snRNA is recognized specifically by the Lsm2-8 complex, a doughnut-like heteroheptameric complex related to the Sm complex found on the snRNPs.


Polyuridylation in Eukaryotes: A 3'-End Modification Regulating RNA Life.

Munoz-Tello P, Rajappa L, Coquille S, Thore S - Biomed Res Int (2015)

Known functions of polyuridylation in the nucleus and in the mitochondria. (a) Functions in the nucleus. U6 snRNA is the only known substrate for polyuridylation in the nucleus by U6 TUTase. Polyuridylation is thought to regenerate the 3′-end of U6 snRNA following its shortening by exonucleases. If this RNA is adenylated, the polyuridylation event is inhibited and the U6 snRNA is degraded. If the RNA is polyuridylated, mature U6 snRNA is produced and incorporated in the splicing complex known as the spliceosome. (b) Function of polyuridylation in the mitochondria of trypanosomes. In order to be properly matured, gRNAs are polyuridylated by RET1 TUTase allowing the gRNA to “guide” the editing reaction. To be translationally competent, mitochondrial mRNAs require addition of a long A/U tail, which is performed by the RET1/KPAP1 complex and coordinated by the KPAF1/KPAF2 complex. The mRNA is then recognized by the ribosome and translation can be started.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4442281&req=5

fig2: Known functions of polyuridylation in the nucleus and in the mitochondria. (a) Functions in the nucleus. U6 snRNA is the only known substrate for polyuridylation in the nucleus by U6 TUTase. Polyuridylation is thought to regenerate the 3′-end of U6 snRNA following its shortening by exonucleases. If this RNA is adenylated, the polyuridylation event is inhibited and the U6 snRNA is degraded. If the RNA is polyuridylated, mature U6 snRNA is produced and incorporated in the splicing complex known as the spliceosome. (b) Function of polyuridylation in the mitochondria of trypanosomes. In order to be properly matured, gRNAs are polyuridylated by RET1 TUTase allowing the gRNA to “guide” the editing reaction. To be translationally competent, mitochondrial mRNAs require addition of a long A/U tail, which is performed by the RET1/KPAP1 complex and coordinated by the KPAF1/KPAF2 complex. The mRNA is then recognized by the ribosome and translation can be started.
Mentions: Until now, the only substrate of uridylation reported in the nucleus is the U6 snRNA (Figure 1). This RNA is uridylated by the U6 TUTase, which is an essential enzyme for cell survival in mammals [64]. SiRNA-mediated silencing of the U6 TUTase leads to U6 snRNA decay, confirming the necessity of uridylation for U6 snRNA stability [64]. U6 TUTase is responsible for the addition or restoration of at least four uridine residues at the 3′-end of U6 snRNA since 3′-end of U6 snRNA is constantly subjected to exonucleases activity [64, 76]. These four U residues form an intramolecular double strand with a stretch of adenines within the U6 snRNA molecule, which is important for mRNA splicing [64]. This uridylation event specifically in the nucleus allows the proper production of a splicing-competent U6 snRNP (Figure 2(a)). Mammalian U6 snRNA uridylation in vivo has been reported with up to 20 nucleotides added at the 3′-end of the RNA molecule [77, 78]. It is important to note that U6 snRNA is also subjected to adenylation and this event inhibits its uridylation (Figure 2(a)) [79]. Moreover, the 3′-end of U6 snRNA is recognized specifically by the Lsm2-8 complex, a doughnut-like heteroheptameric complex related to the Sm complex found on the snRNPs.

Bottom Line: Numerous types of modifications have been characterized, which are generally specific for a given type of RNA such as the CCA addition found in tRNAs.In recent years, the addition of nontemplated uridine nucleotides or uridylation has been shown to occur in various types of RNA molecules and in various cellular compartments with significantly different outcomes.The present review aims at summarizing the current knowledge on the various processes leading to RNA 3'-end uridylation and on their potential impacts in various diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, University of Geneva, 1211 Geneva, Switzerland ; Department of Molecular Therapeutics, The Scripps Research Institute, 110 Scripps Way, Building A Room A265, Jupiter, FL 33458, USA.

ABSTRACT
In eukaryotes, mRNA polyadenylation is a well-known modification that is essential for many aspects of the protein-coding RNAs life cycle. However, modification of the 3' terminal nucleotide within various RNA molecules is a general and conserved process that broadly modulates RNA function in all kingdoms of life. Numerous types of modifications have been characterized, which are generally specific for a given type of RNA such as the CCA addition found in tRNAs. In recent years, the addition of nontemplated uridine nucleotides or uridylation has been shown to occur in various types of RNA molecules and in various cellular compartments with significantly different outcomes. Indeed, uridylation is able to alter RNA half-life both in positive and in negative ways, highlighting the importance of the enzymes in charge of performing this modification. The present review aims at summarizing the current knowledge on the various processes leading to RNA 3'-end uridylation and on their potential impacts in various diseases.

No MeSH data available.