mRNA encoding Sec61β, a tail-anchored protein, is localized on the endoplasmic reticulum.
Although one pathway for the post-translational targeting of tail-anchored proteins to the endoplasmic reticulum (ER) has been well defined, it is unclear whether additional pathways exist. Here, we provide evidence that a subset of mRNAs encoding tail-anchored proteins, including Sec61β and nesprin-2, is partially localized to the surface of the ER in mammalian cells. In particular, Sec61b mRNA can be targeted to, and later maintained on, the ER using both translation-dependent and -independent mechanisms. Our data suggests that this process is independent of p180 (also known as RRBP1), a known mRNA receptor on the ER, and the transmembrane domain recognition complex (TRC) pathway components, TRC40 (also known as ASNA1) and BAT3 (also known as BAG6). In addition, our data indicates that Sec61b mRNA might access translocon-bound ribosomes. Our results show that certain tail-anchored proteins are likely to be synthesized directly on the ER, and this facilitates their membrane insertion. Thus, it is clear that mammalian cells utilize multiple mechanisms to ensure efficient targeting of tail-anchored proteins to the surface of the ER.
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada.
Xianying A
XA
Cui
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada.
Hui
H
Zhang
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada.
Lena
L
Ilan
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada.
Ai Xin
AX
Liu
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada.
Iryna
I
Kharchuk
University of Toronto, Department of Biochemistry, 1 King's College Circle, MSB Room 5336, Toronto, ON, M5S 1A8, Canada alex.palazzo@utoronto.ca.
Alexander F
AF
Palazzo
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000069816:SEC Translocation Channels; D002352:Carrier Proteins
D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000069816:SEC Translocation Channels; C499388:SEC61B protein, human; C485904:SYNE2 protein, human; C000602809:RRBP1 protein, human; D002352:Carrier Proteins
Endoplasmic reticulum; Secretion; Tail-anchored protein; mRNA localization