Academic Integrity: tutoring, explanations, and feedback — we don’t complete graded work or submit on a student’s behalf.

1. The mammalian Ink4A-Arf locus (see PDF) encodes two different proteins involv

ID: 3167314 • Letter: 1

Question

1. The mammalian Ink4A-Arf locus (see PDF) encodes two different proteins involved in preventing tumor formation (tumor suppressor genes). The genes partially overlap and are in different open reading frames. Ink4A is in the +2 frame relative to Arf. They also share a subset of splice sites.

Arrows represent the following splicing signals.

a: Arf  5’ splice site

b: Ink4A5’ splice site

c: Arfand Ink4A3’ splice site

d: Arf and Ink4A5’ splice site

e: Arf and Ink4A3’ splice site

A. Mutant forms of these genes are present in certain human cancers, such as head and neck squamous cell carcinoma, melanoma, lymphoblastic leukemia, and pancreatic ductal adenocarcinoma.

- What type of splicing defect would result in the loss of Arf but not Ink4A?

- What type of splicing defect would result in the loss of Ink4Abut not Arf?

- What type of splicing defect would result in the loss of both Arfand Ink4A?

Arf promoter Ink4A promoter ATG ATG stop stop

Explanation / Answer

Mature mRNA will contain the following segments.

Arf: a b c

Ink4A: b c d e

What type of splicing defect would result in the loss of Arf but not Ink4A?

Defect in splice site that is present only in Arf will result in loss of Arf but not Ink4A. So defect in splicing site 'a' will result in loss of Arf but not Ink4A.

What type of splicing defect would result in the loss of Ink4Abut not Arf?

Defect in splice site that is present only in Ink4A will result in loss of Ink4A but not Arf. Defect in splicing site 'd' or 'e' will result in loss of Ink4A but not Arf.

What type of splicing defect would result in the loss of both Arfand Ink4A?

Defect in splice site that is present commonly in Arf and Ink4A will result in loss of Arf and Ink4A.Defect in splicing site 'b' or 'c' will result in loss of both Ink4A and Arf.