PABPC1 explained

Polyadenylate-binding protein 1 is a protein that in humans is encoded by the PABPC1 gene.^[1] The protein PABP1 binds mRNA and facilitates a variety of functions such as transport into and out of the nucleus, degradation, translation, and stability. There are two separate PABP1 proteins, one which is located in the nucleus (PABPN1) and the other which is found in the cytoplasm (PABPC1). The location of PABP1 affects the role of that protein and its function with RNA.^[2]

Function

The poly(A)-binding protein (PAB or PABP), which is found complexed to the 3' poly(A) tail of eukaryotic mRNA, is required for poly(A) lengthening and the termination of translation. In humans, the PABPs comprise a small nuclear isoform and a conserved gene family of other poly(A)-binding proteins.[supplied by OMIM]^[3]

PABPC1 is usually diffused within the cytoplasm and concentrated at sites of high mRNA concentration such as stress granules, processing bodies, and locations of high translational activity. PABPC1 is also associated with nonsense-mediated mRNA decay (NMD). PABPC1 binds to the poly(A) tail and interact with eIF4G, which stabilizes the circularization of mRNAs. This structure is required for the prevention of mRNA degradation via NMD.^[4]

In the nucleus PABP1 binds to the poly(A) tails of pre-mRNAs to facilitate stability, export, transport, and degradation. PABP1 binding is also required for nuclear-mediated degradation. PABPC1 contains four RNA-recognition motifs (RRMs). The first two, RRM1 and RRM2, bind both α-importin and the poly(A) tail of processed mRNA. This feature prevents mRNA from going back into the nucleus.

Interactions

PABPC1 has been shown to interact with:

• ANAPC5,^[5]
• CNOT7,^[6]
• EIF4G3,
• EIF4G1,^[7]
• GSPT2,^[8]
• PAIP1,^{[9] [10]} and
• PAIP2.^[11]

Further reading

• Görlach M, Burd CG, Dreyfuss G . The mRNA poly(A)-binding protein: localization, abundance, and RNA-binding specificity . Experimental Cell Research . 211 . 2 . 400–7 . April 1994 . 7908267 . 10.1006/excr.1994.1104 . free .
• Campbell LH, Borg KT, Haines JK, Moon RT, Schoenberg DR, Arrigo SJ . Human immunodeficiency virus type 1 Rev is required in vivo for binding of poly(A)-binding protein to Rev-dependent RNAs . Journal of Virology . 68 . 9 . 5433–8 . September 1994 . 8057425 . 236943 . 10.1128/jvi.68.9.5433-5438.1994.
• Huang Y, Carmichael GG . Role of polyadenylation in nucleocytoplasmic transport of mRNA . Molecular and Cellular Biology . 16 . 4 . 1534–42 . April 1996 . 8657127 . 231138 . 10.1128/mcb.16.4.1534.
• Craig AW, Haghighat A, Yu AT, Sonenberg N . Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation . Nature . 392 . 6675 . 520–3 . April 1998 . 9548260 . 10.1038/33198 . 1998Natur.392..520C . 10891925 .
• Afonina E, Stauber R, Pavlakis GN . The human poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm . The Journal of Biological Chemistry . 273 . 21 . 13015–21 . May 1998 . 9582337 . 10.1074/jbc.273.21.13015 . free .
• Imataka H, Gradi A, Sonenberg N . A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation . The EMBO Journal . 17 . 24 . 7480–9 . December 1998 . 9857202 . 1171091 . 10.1093/emboj/17.24.7480 .
• Hornstein E, Git A, Braunstein I, Avni D, Meyuhas O . The expression of poly(A)-binding protein gene is translationally regulated in a growth-dependent fashion through a 5'-terminal oligopyrimidine tract motif . The Journal of Biological Chemistry . 274 . 3 . 1708–14 . January 1999 . 9880551 . 10.1074/jbc.274.3.1708 . free .
• Laroia G, Cuesta R, Brewer G, Schneider RJ . Control of mRNA decay by heat shock-ubiquitin-proteasome pathway . Science . 284 . 5413 . 499–502 . April 1999 . 10205060 . 10.1126/science.284.5413.499 . 1999Sci...284..499L .
• Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T . The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein . The Journal of Biological Chemistry . 274 . 24 . 16677–80 . June 1999 . 10358005 . 10.1074/jbc.274.24.16677 . free .
• Deo RC, Bonanno JB, Sonenberg N, Burley SK . Recognition of polyadenylate RNA by the poly(A)-binding protein . Cell . 98 . 6 . 835–45 . September 1999 . 10499800 . 10.1016/S0092-8674(00)81517-2 . 16247357 . free .
• Féral C, Mattéi MG, Pawlak A, Guellaën G . Chromosomal localization of three human poly(A)-binding protein genes and four related pseudogenes . Human Genetics . 105 . 4 . 347–53 . October 1999 . 10543404 . 1865476 . 10.1007/s004399900148 .
• Grosset C, Chen CY, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu AB . A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex . Cell . 103 . 1 . 29–40 . September 2000 . 11051545 . 10.1016/S0092-8674(00)00102-1 . 18135412 . free .
• Khaleghpour K, Svitkin YV, Craig AW, DeMaria CT, Deo RC, Burley SK, Sonenberg N . Translational repression by a novel partner of human poly(A) binding protein, Paip2 . Molecular Cell . 7 . 1 . 205–16 . January 2001 . 11172725 . 10.1016/S1097-2765(01)00168-X . free .
• Bushell M, Wood W, Carpenter G, Pain VM, Morley SJ, Clemens MJ . Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages . The Journal of Biological Chemistry . 276 . 26 . 23922–8 . June 2001 . 11274152 . 10.1074/jbc.M100384200 . free .
• Féral C, Guellaën G, Pawlak A . Human testis expresses a specific poly(A)-binding protein . Nucleic Acids Research . 29 . 9 . 1872–83 . May 2001 . 11328870 . 37253 . 10.1093/nar/29.9.1872 .
• Khaleghpour K, Kahvejian A, De Crescenzo G, Roy G, Svitkin YV, Imataka H, O'Connor-McCourt M, Sonenberg N . Dual interactions of the translational repressor Paip2 with poly(A) binding protein . Molecular and Cellular Biology . 21 . 15 . 5200–13 . August 2001 . 11438674 . 87244 . 10.1128/MCB.21.15.5200-5213.2001 .
• Woods AJ, Roberts MS, Choudhary J, Barry ST, Mazaki Y, Sabe H, Morley SJ, Critchley DR, Norman JC . Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells . The Journal of Biological Chemistry . 277 . 8 . 6428–37 . February 2002 . 11704675 . 10.1074/jbc.M109446200 . free .
• Lee J, Bedford MT . PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays . EMBO Reports . 3 . 3 . 268–73 . March 2002 . 11850402 . 1084016 . 10.1093/embo-reports/kvf052 .
• Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ . Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis . RNA . 8 . 4 . 426–39 . April 2002 . 11991638 . 1370266 . 10.1017/S1355838202021088 .

Notes and References

1. Grange T, de Sa CM, Oddos J, Pictet R . Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif . Nucleic Acids Research . 15 . 12 . 4771–87 . June 1987 . 2885805 . 305917 . 10.1093/nar/15.12.4771 .
2. Gray NK, Hrabálková L, Scanlon JP, Smith RW . Poly(A)-binding proteins and mRNA localization: who rules the roost? . en . Biochemical Society Transactions . 43 . 6 . 1277–84 . December 2015 . 26614673 . 10.1042/BST20150171 . free .
3. Web site: Entrez Gene: PABPC1 poly(A) binding protein, cytoplasmic 1.
4. Fatscher T, Boehm V, Weiche B, Gehring NH . The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay . en . RNA . 20 . 10 . 1579–92 . October 2014 . 25147240 . 4174440 . 10.1261/rna.044933.114 .
5. Koloteva-Levine N, Pinchasi D, Pereman I, Zur A, Brandeis M, Elroy-Stein O . The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ribosome entry site-mediated translation . Molecular and Cellular Biology . 24 . 9 . 3577–87 . May 2004 . 15082755 . 387753 . 10.1128/mcb.24.9.3577-3587.2004 .
6. Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, Tsujimoto M, Suzuki T, Katada T, Hoshino S . Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases . Genes & Development . 21 . 23 . 3135–48 . December 2007 . 18056425 . 2081979 . 10.1101/gad.1597707 .
7. Imataka H, Gradi A, Sonenberg N . A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation . The EMBO Journal . 17 . 24 . 7480–9 . December 1998 . 9857202 . 1171091 . 10.1093/emboj/17.24.7480 .
8. Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T . The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein . The Journal of Biological Chemistry . 274 . 24 . 16677–80 . June 1999 . 10358005 . 10.1074/jbc.274.24.16677 . free .
9. Roy G, De Crescenzo G, Khaleghpour K, Kahvejian A, O'Connor-McCourt M, Sonenberg N . Paip1 interacts with poly(A) binding protein through two independent binding motifs . Molecular and Cellular Biology . 22 . 11 . 3769–82 . June 2002 . 11997512 . 133836 . 10.1128/mcb.22.11.3769-3782.2002 .
10. Craig AW, Haghighat A, Yu AT, Sonenberg N . Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation . Nature . 392 . 6675 . 520–3 . April 1998 . 9548260 . 10.1038/33198 . 1998Natur.392..520C . 10891925 .
11. Khaleghpour K, Kahvejian A, De Crescenzo G, Roy G, Svitkin YV, Imataka H, O'Connor-McCourt M, Sonenberg N . Dual interactions of the translational repressor Paip2 with poly(A) binding protein . Molecular and Cellular Biology . 21 . 15 . 5200–13 . August 2001 . 11438674 . 87244 . 10.1128/MCB.21.15.5200-5213.2001 .