Alexander F. Palazzo

Alexander F. Palazzo

Associate Professor

BSc, McGill University, 1997
PhD, Columbia University, 2003
Postdoc, Harvard Medical School, 2003-2009

Address MaRS, West Tower, Suite 1500
661 University Ave.

Toronto, ON M5G 1M1
Lab Palazzo Lab
Lab Phone 416-978-7450
Office Phone 416-978-7234
Email alex.palazzo@utoronto.ca

Alexander Francis Palazzo was born and raised in Montreal, Canada. As a graduate student in Gregg Gundersen’s laboratory at Columbia University, he discovered two major pathways that regulate cell polarity in migrating fibroblasts. After receiving his PhD in 2003, he moved to Tom Rapoport’s laboratory at Harvard Medical School where he was a Jane Coffin Childs Postdoctoral Fellow. There he investigated how newly synthesized mRNA is exported from the nucleus and then targeted to specific sites in the cytoplasm of mammalian cells, such as the surface of the endoplasmic reticulum. In 2009 he started his lab in the Biochemistry Department.

Besides his work on mRNA export and localization, Dr. Palazzo is interested in how biological information is extracted from the mammalian genome. He has published several well regarded reviews on how mRNA processing and nuclear export is used to sort useful information from a genome that is mostly filled with junk DNA.

Dr. Palazzo has received several awards and is an editorial board member of the journal PLoS One.

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Research Lab

In the Palazzo lab we are studying the rules that govern whether an RNA molecule is exported from the nucleus and subsequently transported to specific subcellular regions, or whether it is retained in the nucleus and degraded. We use a combination of cell biological, biochemical and computational methods in order to gain insight into these fundamental processes.

Learn more: Palazzo Lab

Research Description

Nuclear Export and Localization of mRNA

ER Nucleus

A human cell line showing the endoplasmic reticulum (yellow) and nucleus (blue).

Gene expression plays a critical role in regulating and modifying various cellular functions, which impact on processes such as development and homeostasis. Gene activation begins in the nucleus, where DNA is transcribed into a nascent transcript that is processed so that non-coding introns are removed by the splicesome, and a cap and poly-A tail are added to the beginning and end of the RNA, respectively. Once processing is complete, the mature messenger RNA (mRNA) is exported to the cytoplasm where it localizes to distinct subcellular sites. For example in higher eukaryotes, mRNAs coding for secreted and membrane bound proteins are targeted to the surface of the endoplasmic reticulum (ER).

Our lab utilizes sophisticated cell manipulation protocols, such as nuclear microinjection, in order to figure out:

1) How are mRNAs exported from the nucleus?
2) How are mRNAs localized to their proper subcellular destination, such as the endoplasmic reticulum?
3) How does mRNA translation in the cytosol differ from translation on the endoplasmic reticulum?

Nuclear export of mRNA

We are currently trying to figure out how meaningful information is extracted from our genome, which is mostly comprised of junk DNA. A central player in cellular information processing is the mRNA nuclear export machinery.

All RNA synthesis occurs in the nucleus. However, it is clear that only certain types of RNA are allowed to be exported to the cytoplasm. We are trying to define:

Ftz mRNA transits through speckles in preparation for nuclear export.

Ftz mRNA transits through nuclear speckles (marked by SC35 and Aly) in preparation for nuclear export.

1) the rules that dictate whether any given mRNA is exported to the cytoplasm, retained in the nucleus or degraded

2) the underlying mechanisms that enforce these various fates.

One key concept is that all RNAs are packaged into larger ribonucleoprotein (RNP) complexes. These complexes may vary considerably between different types of mRNA. We are trying to determine how and where these complexes are assembled and modified throughout the course of an mRNAs’ lifetime.

Targeting of mRNAs to the endoplasmic reticulum

image337

p180 (green) acts as an mRNA (red) receptor on the ER.

Secretory and membrane-bound proteins are synthesized from mRNAs that are localized to the surface of the endoplasmic reticulum (ER). We have discovered that the ER contains mRNA receptors that aid in this process. We hope to uncover:

1) the mechanism by which mRNA receptors facilitate ER-association of certain mRNAs

2) the elements within these mRNAs that determines their targeting to the ER

3) differences between the composition of cytoplasmic and ER-bound ribonucleoprotein complexes.

Differences between translation in the cytosol and on the endoplasmic reticulum

It has been long known that translation in the cytosol and on the surface of the endoplasmic reticulum differ, but the underlying reasons for this are mysterious. We have identified differences between the proteome of cytosolic and endoplasmic reticulum-associated polysomes by mass spectrometry. We are currently investigating how these differences influence mRNA translation in these two compartments.

Awards & Distinctions

2014 — Ontario Early Researcher Award
2013 — Canadian Institute for Health Research New Investigator Award
2011 — Connaught New Researcher Award
2004 — Jane Coffin Childs Memorial Research Fund Postdoctoral Fellow

Courses Taught

BCH479H Advanced Seminar in Biochemistry
BCH2024H Special Topics in Eukaryotic Gene Expression
BCH473Y Advanced Research Project in Biochemistry
BCH448H Structure and Function of the Nucleus

Extra-Departmental Courses

LMP1404H Molecular & Cellular Mechanisms of Disease

Publications

View all publications on PubMed

Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements
Akef A, Lee ES, Palazzo AF
RNA 2015 21(11):1908-20.  Read

mRNA encoding Sec61β, a tail-anchored protein, is localized on the endoplasmic reticulum
Cui XA, Zhang H, Ilan L, Liu AX, Kharchuk I, Palazzo AF
J Cell Sci. 2015 128(18):3398-410.  Read

Non-coding RNA: what is functional and what is junk?
Palazzo AF, Lee ES.
Front Genet. 2015 6(2):1-11.  Read

The consensus 5' splice site motif inhibits mRNA nuclear export.
Lee ES, Akef A, Mahadevan K, Palazzo AF.
PLoS One. 2015 10(3):e0122743.  Read

Sumoylation is Required for the Cytoplasmic Accumulation of a Subset of mRNAs.
Zhang H, Mahadevan K, Palazzo AF.
Genes. 2014 5(4):982-1000.  Read

The case for junk DNA.
Palazzo AF, Gregory TR.
PLoS Genetics 2014 10(5):e1004351.  Read

Localization of mRNAs to the endoplasmic reticulum.
Cui XA, Palazzo AF.
Wiley Interdiscip Rev RNA. 2014 5(4):481-92.  Read

RanBP2/Nup358 potentiates the translation of a subset of mRNAs encoding secretory proteins.
Mahadevan K, Zhang H, Akef A, Cui XA, Gueroussov S, Cenik C, Roth FP, Palazzo AF
PLoS Biology 2013 11(4):e1001545.  Read

Identification of a region within the placental alkaline phosphatase mRNA that mediates p180-dependent targeting to the endoplasmic reticulum.
Cui XA, Zhang Y, Hong SJ, Palazzo AF.
J Biol Chem. 2013 288(41):29633-41.  Read

Trafficking of mRNAs containing ALREX-promoting elements through nuclear speckles.
Akef A, Zhang H, Masuda S, Palazzo AF.
Nucleus. 2013 4(4):326-40.  Read

p180 promotes the ribosome-independent localization of a subset of mRNA to the endoplasmic reticulum.
Cui XA, Zhang H, Palazzo AF
PLoS Biology 2012 10(5):e1001336.  Read

Nuclear export as a key arbiter of "mRNA identity" in eukaryotes.
Palazzo AF, Akef A.
Biochim Biophys Acta. 2012 1819(6):566-77.  Read

Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes.
Cenik C, Chua HN, Zhang H, Tarnawsky SP, Akef A, Derti A, Tasan M, Moore MJ, Palazzo AF, Roth FP.
PLoS Genetics 2011 7(4):e1001366.  Read

Mechanisms determining the morphology of the peripheral ER.
Shibata Y, Shemesh T, Prinz WA, Palazzo AF, Kozlov MM, Rapoport TA.
Cell. 2010 143(5):774-88.  Read