Here, I share both the tools and knowledge I used to score a 270 on the USMLE Step 1 exam. How did I do it? Since the USMLE Step 1 exam tests your understanding and application of knowledge rather than memorization, the students who have the best understanding of the processes they learn will do the best.
As a teaser, I will start with the questions you will be able to answer by the end of this. By understanding these “pathogenesis to presentation” questions, where you can create a narrative between the pathophysiology to the way that they present, you will in fact be able to recall the related information involved without having to memorize it! Here are the questions:
- What does “naked viral genome infectivity” mean?
- Naked viral genome infectivity – what naked viral genomes are infective and why?
- What are the exceptions and why?
What is the process of transcription? What do you call the product of this?
DNA → RNA (specifically, mRNA, or “messenger” RNA)
What is the process of translation? What is the translation “start” signal?
mRNA → protein
AUG = start signal
What direction is RNA synthesized? (5’ → 3’ or 3’ → 5’)
5’ → 3’
What direction is RNA read? (5’ → 3’ or 3’ → 5’)
5’ → 3’
RNA processing (eukaryotes) - what are the major steps (3)
Capping on 5′ end (7-methylguanosine)Polyadenylation on 3′ end (~200 A’s)Splicing out of introns
What is the purpose of capping?
Recall that RNA is VERY easily degraded, so must PROTECT RNA
5′ cap – protect it from being degraded by exonucleases (“exo” because it cleaves RNA beginning from the “outside” – i.e. ends; as opposed to “endo”nucleases which cleave the RNA strands from the middle)
What is the purpose of and polyadenylation of RNA? What end does this occur at?
Recall: as long as the RNA persists in the cytosol, you can make proteins out of it. HOWEVER, you want to LIMIT the amount of proteins that you make from any one mRNA.
3′ polyA tail – the 5’ end of the RNA is protected by the 5’ cap. However, exonucleases will degrade the RNA starting at the 3’ end, thus having a longer 3’ “tail” will require MORE time for exonucleases to degrade the RNA.
Basically sets halflife, as it will take a while for exonucleases to degrade it
Initiation of translation - what is the mechanism?
Small subunit binds upstream on 5’ cap, then proceeds downstream until AUG (start codon) is encounteredProkaryotic small subunit: 30S. Eukaryotic small subunit: 40S.Joined by the large subunit, initiation factors (IFs), and the initiator tRNA (Met or fMet) enters the P-siteProkaryotic large subunit: 50S. Eukaryotic large subunit: 60S.Initiator tRNA is the only tRNA that can bind to the P-site; all others bind to A-site
What does it mean to be a +RNA virus?
Virus whose RNA genome can be translated directly into a protein.
Recall that in RNA, messenger RNA (mRNA) is what can be translated directly into a protein, while the complementary strand itself does not code a protein to be synthesized – but it is “complementary” to a strand that can be. Thus, +RNA viruses are those whose genome is essentially mRNA.
What does it mean to be a -RNA virus?
Just like +RNA is mRNA, if the virus is -RNA, its genome cannot be translated directly into a protein.
RNA polymerase – what is the alternative term?
DNA-dependent, RNA polymerase
In other words, it READS DNA, and PRODUCES RNA
Alternative term for what? (HINT: turn this into a “reverse” Anki card)
Reverse transcriptase – what is the alternative term?
RNA-dependent, DNA polymerase
In other words, it READS RNA, and produces DNA
Alternative term for what? (HINT: turn this into a “reverse” Anki card)
DNA polymerase – what is the alternative term?
DNA-dependent, DNA polymerase
In other words, it READS DNA, and produces DNA
Alternative term for what? (HINT: turn this into a “reverse” Anki card)
What would you call the enzyme that turns –RNA → +RNA?
RNA-dependent RNA polymerase
What action would this have?
*NOTE: despite the fact that the polymerase is still technically an RNA polymerase, it is NOT what is commonly referred to as an “RNA polymerase” in common parlance. “RNA polymerase” refers to a DNA-dependent RNA polymerase.
What does “naked viral genome infectivity” mean?
If I took the naked viral genome (i.e. ONLY the genetic material, and NOT the envelope/capsid) and injected it into a cell, it could produce viral progeny
Wait!
It is strongly recommended that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot, the more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Ready for the answers?
If I injected the naked viral genome of a dsDNA virus into a cell, could that cell become “infective” (i.e. produce viral particles)? Why or why not?
Typically, it IS infective. This is because the dsDNA can be recognized by our own DNA/RNA polymerases, so can be transcribed/translated by our own protein machinery.
Naked viral genome infectivity – what naked viral genomes are infective and why?
dnDNA (dsDNA can be recognized by our own DNA/RNA polymerases, so can be transcribed/translated by our own protein machinery)+RNA – infective because it’s basically mRNA (i.e. your small ribosomal subunit would recognize it, find the AUG start codon, and begin translation AS IF IT WERE YOUR OWN mRNA)
What are the exceptions to naked viral genome classes that are infective? Why?
dsDNA viruses CAN, except for Pox (requires own polymerase) and Hepadna (presumably because it is only partially dsDNA)
NOTE: ALL +RNA viruses’ naked genomes are infective
What naked viral genome classes are NOT infective? Why?
-RNA – recall that –RNA is NOT mRNA, but rather the complementary strand (i.e. you need an RNA-dependent RNA polymerase to convert it to mRNA to be translated)
ssDNA – also requires its own polymerase
What should you do next?
- Turn the narrative, “Pathogenesis to Presentation” questions into Anki cards by copy/pasting the question/answer into the “Front” and “Back” fields in Anki. Do the same for the fundamental facts that you were unfamiliar with, to maximize your chances of USMLE Step 1 success! Remember: the USMLE is a test of understanding, so the better you can understand these questions, the better your score!
- Add reverse cards when appropriate to your Anki cards
- Re-word the questions/explanations as desired, and BOLD the important text to make it easier to review in the future
- Learn something new? Something unclear? Comment below!
- If you liked this post, please consider sharing it on Facebook/Twitter! I judge the utility of these posts by the number of comments / shares they receive, so if you’d like more, or would like a particular topic addressed, please let us know!
