The expanding world of RNAs 2

Question 1

Does gene transcription always end up in protein?

Answer 1

No! 70–90% of the genome is transcribed and less than 3% of nuclear DNA encodes proteins
We have much more non-coding-RNAs
Virtually all biological process is regulated by ncRNAs

Question 2

What is DiGeorge syndrome?

Answer 2

Homozygous mutations resulting in embryonic lethality (hemizygous deletion is viable)
One of the most common human genetic deletion disorders
Disorder: dgcr8-deficiency leading to altered miRNA
Symptoms: behavioral and cognitive deficiency

Question 3

What is DICER1 syndrome?

Answer 3

Pleuropulmonary blastoma familial tumor
Caused by Dicer enzyme mutation which cleaves pre-miRNA to form miRNA duplexes
Symptom: pediatric tumor of the pituitary gland (accompanied with multi-organ tumor)

Question 4

What is Feingold syndrome 2?

Answer 4

Hemizygous germline deletion of the MIR17HG microRNA-gene
Autosomal dominant inheritance
Symptoms: short stature, variable combinations of craniofacial abnormalities, microcephaly, limb and digit malformations, gastrointestinal atresia and learning disabilities

Question 5

What can be said on alterations in microRNA-profiles in cancer cells?

Answer 5

Deregulation of microRNAs in all types of cancers
Different types of cancers can be discriminated based on microRNA profiles with high accuracy
Malignant phenotype of some cancers can depend on the activity of a single miRNA

Question 6

What can be said on tumor suppressor miRNAs?

Answer 6

• target proto-oncogenes

* often downregulated in cancer

Question 7

What can be said on oncogenic miRNAs?

Answer 7

• target tumor suppressor genes
• often upregulated in cancer
• allows the uncontrolled expression of oncogenes

Question 8

What can be said on Melanoma (cell of origin, primary risk factors,…)?

Answer 8

• One of the fastest increasing cancer-types in Sweden
• Cell of origin: melanocyte (pigment-producing cell)
• Primary risk factors: cumulative UV-exposure and fair skin (accumulating genetic alterations which provide selective growth advantage)

Question 9

What can be said on miRNA-203 in metastatic melanoma

Answer 9

Decreased, leading to poor survival of patients

Normally, suppresses primary melanoma growth

Question 10

What are the potential clinical applications of non-coding RNAs?

Answer 10

DIAGNOSTIC POTENTIAL: frequently expressed at altered levels in diseased tissues (miRNAs potential biomarkers)
THERAPEUTIC POTENTIAL: administration of ncRNAs/inhibitors induces a therapeutic response by blocking or reducing tumor growth