Your lab has been studying a specific lymphoma in which the chromatin-associated protein High Mobility Group A2 (Hmga2) is implicated. The gene is known to be expressed in a wide variety of benign and malignant tumors. Transgenic mice overexpressing wild-type Hmga2 develop abdominal lipomatosis, then lymphomas, pituitary adenomas, and lung adenomas. When screening for hmga2 expression in different human tumor samples you identify a hmga2 sequence that seems prematurely terminated due to a chromosomal rearrangement. You did notice that the Hmga2 protein was over-expressed in those human tumor samples.

Your task is to

1. Characterize this Hmga2 variant to determine how the chromosomal rearrangement is affecting both the mRNA transcript and protein.

- which exons of Hmga2 are affected?

- check in a protein domain database if specific domains of Hmga2 are disrupted by the translocation?

2. Given, what you learned from point 1, you decide to look for cis-regulatory elements that may be responsible for the increased expression, since you suddenly remember a class from yesterday describing a class of short RNAs involved in translational inhibition.

- summarize which microRNAs that are your top candidates using multiple micorRNA target site databases.

Useful Resources:

- UCSC Genome Browser

- BLAT and BLAST

- SMART, BLOCKS or http://harvester.embl.de

- Targetscan, Targetrank and Miranda

- miRBase

-- RickardSandberg - 14 May 2008