Regulation of Mammalian Poly(A) Polymerase Activity

Poly(A) polymerase (PAP) is the enzyme catalyzing the synthesis of the adenine tail to the 3’-end of mRNA. This A-tail is present on the majority of the primary RNA transcripts of protein-coding genes, and is important for mRNA stability, export to the cytoplasm and translation. Therefore, PAP is a key regulator of eukaryotic gene expression. This thesis describes the heterogeneity of PAP and the functional significance of multiple isoforms of PAP. PAP exists in many different isoforms generated by three different mechanisms, gene duplication, alternative mRNA processing and post-translational modification. In HeLa cell extracts three different forms of PAP being 90, 100 and 106 kDa in size have been detected, where the 106 kDa isoform is a phosphorylated version of the 100 kDa species. It is shown that the N-terminal region of PAP contains a region required for catalysis, while the C-terminal end is important for the interaction with the cleavage and polyadenylation specificity factor (CPSF). Interestingly, it was found that also the extreme…


Nuclear polyadenylation in mammalian cells
Cis-acting elements of the polyadenylation machinery
Trans-acting factors of the polyadenylation machinery
3’-end processing
The cleavage reaction
Synthesis of the poly(A) tail
Crosstalk between polyadenylation and other mRNA processing events
Capping and polyadenylation
Splicing and polyadenylation
Termination of transcription and polyadenylation
Poly(A) polymerase
Structure and motifs of mammalian PAP
Specificity for ATP
PAP isoforms
Expression profile and sub-cellular localisation of PAP isoforms
Regulation of nuclear PAP activity
Regulation of PAP activity through its C-terminal
Regulation of poly(A) polymerase through its N-terminal
Regulation of poly(A) polymerase through phosphorylation
Poly(A) polymerase as a therapeutic target

Author: Thuresson, Ann-Charlotte

Source: Uppsala University Library

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